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"text": "\n171373\nGenetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.\n\nRhodes, CJ\n\nBatai, K\n\nBleda, M\n\nHaimel, M\n\nSouthgate, L\n\nGermain, M\n\nPauciulo, MW\n\nHadinnapola, C\n\nAman, J\n\nGirerd, B\n\nArora, A\n\nKnight, J\n\nHanscombe, KB\n\nKarnes, JH\n\nKaakinen, M\n\nGall, H\n\nUlrich, A\n\nHarbaum, L\n\nCebola, I\n\nFerrer, J\n\nLutz, K\n\nSwietlik, EM\n\nAhmad, F\n\nAmouyel, P\n\nArcher, SL\n\nArgula, R\n\nAustin, ED\n\nBadesch, D\n\nBakshi, S\n\nBarnett, C\n\nBenza, R\n\nBhatt, N\n\nBogaard, HJ\n\nBurger, CD\n\nChakinala, M\n\nChurch, C\n\nCoghlan, JG\n\nCondliffe, R\n\nCorris, PA\n\nDanesino, C\n\nDebette, S\n\nElliott, CG\n\nElwing, J\n\nEyries, M\n\nFortin, T\n\nFranke, A\n\nFrantz, RP\n\nFrost, A\n\nGarcia, JGN\n\nGhio, S\n\nGhofrani, HA\n\nGibbs, JSR\n\nHarley, J\n\nHe, H\n\nHill, NS\n\nHirsch, R\n\nHouweling, AC\n\nHoward, LS\n\nIvy, D\n\nKiely, DG\n\nKlinger, J\n\nKovacs, G\n\nLahm, T\n\nLaudes, M\n\nMachado, RD\n\nMacKenzie Ross, RV\n\nMarsolo, K\n\nMartin, LJ\n\nMoledina, S\n\nMontani, D\n\nNathan, SD\n\nNewnham, M\n\nOlschewski, A\n\nOlschewski, H\n\nOudiz, RJ\n\nOuwehand, WH\n\nPeacock, AJ\n\nPepke-Zaba, J\n\nRehman, Z\n\nRobbins, I\n\nRoden, DM\n\nRosenzweig, EB\n\nSaydain, G\n\nScelsi, L\n\nSchilz, R\n\nSeeger, W\n\nShaffer, CM\n\nSimms, RW\n\nSimon, M\n\nSitbon, O\n\nSuntharalingam, J\n\nTang, H\n\nTchourbanov, AY\n\nThenappan, T\n\nTorres, F\n\nToshner, MR\n\nTreacy, CM\n\nVonk Noordegraaf, A\n\nWaisfisz, Q\n\nWalsworth, AK\n\nWalter, RE\n\nWharton, J\n\nWhite, RJ\n\nWilt, J\n\nWort, SJ\n\nYung, D\n\nLawrie, A\n\nHumbert, M\n\nSoubrier, F\n\nTrégouët, DA\n\nProkopenko, I\n\nKittles, R\n\nGräf, S\n\nNichols, WC\n\nTrembath, RC\n\nDesai, AA\n\nMorrell, NW\n\nWilkins, MR\n\nUK NIHR BioResource Rare Diseases Consortium\n\nUK PAH Cohort Study Consortium\n\nUS PAH Biobank Consortium\n\nBeiträge in Fachzeitschriften\nISI:000459820400019\n30527956.0\n10.1016/S2213-2600(18)30409-0\nPMC6391516\nRare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.\n We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.\n A locus near SOX17 (rs10103692, odds ratio 1·80 [95% CI 1·55-2·08], p=5·13 × 10-15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 [1·42-1·71], p=7·65 × 10-20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 [1·25-1·48], p=1·69 × 10-12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years [95% CI 12·07 to >13·50]) that of those with the T/T genotype (6·97 years [6·02-8·05]), despite similar baseline disease severity.\n This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.\n UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR.\n Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.\n\nKovacs, Gabor\n\nOlschewski, Andrea\n\nOlschewski, Horst\n\n\n"
},
{
"text": "\n181684\nThe genetic architecture of the human cerebral cortex.\n\nGrasby, KL\n\nJahanshad, N\n\nPainter, JN\n\nColodro-Conde, L\n\nBralten, J\n\nHibar, DP\n\nLind, PA\n\nPizzagalli, F\n\nChing, CRK\n\nMcMahon, MAB\n\nShatokhina, N\n\nZsembik, LCP\n\nThomopoulos, SI\n\nZhu, AH\n\nStrike, LT\n\nAgartz, I\n\nAlhusaini, S\n\nAlmeida, MAA\n\nAlnæs, D\n\nAmlien, IK\n\nAndersson, M\n\nArd, T\n\nArmstrong, NJ\n\nAshley-Koch, A\n\nAtkins, JR\n\nBernard, M\n\nBrouwer, RM\n\nBuimer, EEL\n\nBülow, R\n\nBürger, C\n\nCannon, DM\n\nChakravarty, M\n\nChen, Q\n\nCheung, JW\n\nCouvy-Duchesne, B\n\nDale, AM\n\nDalvie, S\n\nde Araujo, TK\n\nde Zubicaray, GI\n\nde Zwarte, SMC\n\nden Braber, A\n\nDoan, NT\n\nDohm, K\n\nEhrlich, S\n\nEngelbrecht, HR\n\nErk, S\n\nFan, CC\n\nFedko, IO\n\nFoley, SF\n\nFord, JM\n\nFukunaga, M\n\nGarrett, ME\n\nGe, T\n\nGiddaluru, S\n\nGoldman, AL\n\nGreen, MJ\n\nGroenewold, NA\n\nGrotegerd, D\n\nGurholt, TP\n\nGutman, BA\n\nHansell, NK\n\nHarris, MA\n\nHarrison, MB\n\nHaswell, CC\n\nHauser, M\n\nHerms, S\n\nHeslenfeld, DJ\n\nHo, NF\n\nHoehn, D\n\nHoffmann, P\n\nHolleran, L\n\nHoogman, M\n\nHottenga, JJ\n\nIkeda, M\n\nJanowitz, D\n\nJansen, IE\n\nJia, T\n\nJockwitz, C\n\nKanai, R\n\nKarama, S\n\nKasperaviciute, D\n\nKaufmann, T\n\nKelly, S\n\nKikuchi, M\n\nKlein, M\n\nKnapp, M\n\nKnodt, AR\n\nKrämer, B\n\nLam, M\n\nLancaster, TM\n\nLee, PH\n\nLett, TA\n\nLewis, LB\n\nLopes-Cendes, I\n\nLuciano, M\n\nMacciardi, F\n\nMarquand, AF\n\nMathias, SR\n\nMelzer, TR\n\nMilaneschi, Y\n\nMirza-Schreiber, N\n\nMoreira, JCV\n\nMühleisen, TW\n\nMüller-Myhsok, B\n\nNajt, P\n\nNakahara, S\n\nNho, K\n\nOlde Loohuis, LM\n\nOrfanos, DP\n\nPearson, JF\n\nPitcher, TL\n\nPütz, B\n\nQuidé, Y\n\nRagothaman, A\n\nRashid, FM\n\nReay, WR\n\nRedlich, R\n\nReinbold, CS\n\nRepple, J\n\nRichard, G\n\nRiedel, BC\n\nRisacher, SL\n\nRocha, CS\n\nMota, NR\n\nSalminen, L\n\nSaremi, A\n\nSaykin, AJ\n\nSchlag, F\n\nSchmaal, L\n\nSchofield, PR\n\nSecolin, R\n\nShapland, CY\n\nShen, L\n\nShin, J\n\nShumskaya, E\n\nSønderby, IE\n\nSprooten, E\n\nTansey, KE\n\nTeumer, A\n\nThalamuthu, A\n\nTordesillas-Gutiérrez, D\n\nTurner, JA\n\nUhlmann, A\n\nVallerga, CL\n\nvan der Meer, D\n\nvan Donkelaar, MMJ\n\nvan Eijk, L\n\nvan Erp, TGM\n\nvan Haren, NEM\n\nvan Rooij, D\n\nvan Tol, MJ\n\nVeldink, JH\n\nVerhoef, E\n\nWalton, E\n\nWang, M\n\nWang, Y\n\nWardlaw, JM\n\nWen, W\n\nWestlye, LT\n\nWhelan, CD\n\nWitt, SH\n\nWittfeld, K\n\nWolf, C\n\nWolfers, T\n\nWu, JQ\n\nYasuda, CL\n\nZaremba, D\n\nZhang, Z\n\nZwiers, MP\n\nArtiges, E\n\nAssareh, AA\n\nAyesa-Arriola, R\n\nBelger, A\n\nBrandt, CL\n\nBrown, GG\n\nCichon, S\n\nCurran, JE\n\nDavies, GE\n\nDegenhardt, F\n\nDennis, MF\n\nDietsche, B\n\nDjurovic, S\n\nDoherty, CP\n\nEspiritu, R\n\nGarijo, D\n\nGil, Y\n\nGowland, PA\n\nGreen, RC\n\nHäusler, AN\n\nHeindel, W\n\nHo, BC\n\nHoffmann, WU\n\nHolsboer, F\n\nHomuth, G\n\nHosten, N\n\nJack, CR\n\nJang, M\n\nJansen, A\n\nKimbrel, NA\n\nKolskår, K\n\nKoops, S\n\nKrug, A\n\nLim, KO\n\nLuykx, JJ\n\nMathalon, DH\n\nMather, KA\n\nMattay, VS\n\nMatthews, S\n\nMayoral Van Son, J\n\nMcEwen, SC\n\nMelle, I\n\nMorris, DW\n\nMueller, BA\n\nNauck, M\n\nNordvik, JE\n\nNöthen, MM\n\nO´Leary, DS\n\nOpel, N\n\nMartinot, MP\n\nPike, GB\n\nPreda, A\n\nQuinlan, EB\n\nRasser, PE\n\nRatnakar, V\n\nReppermund, S\n\nSteen, VM\n\nTooney, PA\n\nTorres, FR\n\nVeltman, DJ\n\nVoyvodic, JT\n\nWhelan, R\n\nWhite, T\n\nYamamori, H\n\nAdams, HHH\n\nBis, JC\n\nDebette, S\n\nDecarli, C\n\nFornage, M\n\nGudnason, V\n\nHofer, E\n\nIkram, MA\n\nLauner, L\n\nLongstreth, WT\n\nLopez, OL\n\nMazoyer, B\n\nMosley, TH\n\nRoshchupkin, GV\n\nSatizabal, CL\n\nSchmidt, R\n\nSeshadri, S\n\nYang, Q\n\nAlzheimer’s Disease Neuroimaging Initiative\n\nCHARGE Consortium\n\nEPIGEN Consortium\n\nIMAGEN Consortium\n\nSYS Consortium\n\nParkinson’s Progression Markers Initiative\n\nAlvim, MKM\n\nAmes, D\n\nAnderson, TJ\n\nAndreassen, OA\n\nArias-Vasquez, A\n\nBastin, ME\n\nBaune, BT\n\nBeckham, JC\n\nBlangero, J\n\nBoomsma, DI\n\nBrodaty, H\n\nBrunner, HG\n\nBuckner, RL\n\nBuitelaar, JK\n\nBustillo, JR\n\nCahn, W\n\nCairns, MJ\n\nCalhoun, V\n\nCarr, V\n\nBeiträge in Fachzeitschriften\nISI:000522167400044\n32193296.0\n10.1126/science.aay6690\nPMC7295264\nThe cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51, 65 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.\n Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.\n\nHofer, Edith\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n165104\nGenome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.\n\nJustice, AE\n\nWinkler, TW\n\nFeitosa, MF\n\nGraff, M\n\nFisher, VA\n\nYoung, K\n\nBarata, L\n\nDeng, X\n\nCzajkowski, J\n\nHadley, D\n\nNgwa, JS\n\nAhluwalia, TS\n\nChu, AY\n\nHeard-Costa, NL\n\nLim, E\n\nPerez, J\n\nEicher, JD\n\nKutalik, Z\n\nXue, L\n\nMahajan, A\n\nRenström, F\n\nWu, J\n\nQi, Q\n\nAhmad, S\n\nAlfred, T\n\nAmin, N\n\nBielak, LF\n\nBonnefond, A\n\nBragg, J\n\nCadby, G\n\nChittani, M\n\nCoggeshall, S\n\nCorre, T\n\nDirek, N\n\nEriksson, J\n\nFischer, K\n\nGorski, M\n\nNeergaard Harder, M\n\nHorikoshi, M\n\nHuang, T\n\nHuffman, JE\n\nJackson, AU\n\nJustesen, JM\n\nKanoni, S\n\nKinnunen, L\n\nKleber, ME\n\nKomulainen, P\n\nKumari, M\n\nLim, U\n\nLuan, J\n\nLyytikäinen, LP\n\nMangino, M\n\nManichaikul, A\n\nMarten, J\n\nMiddelberg, RPS\n\nMüller-Nurasyid, M\n\nNavarro, P\n\nPérusse, L\n\nPervjakova, N\n\nSarti, C\n\nSmith, AV\n\nSmith, JA\n\nStančáková, A\n\nStrawbridge, RJ\n\nStringham, HM\n\nSung, YJ\n\nTanaka, T\n\nTeumer, A\n\nTrompet, S\n\nvan der Laan, SW\n\nvan der Most, PJ\n\nVan Vliet-Ostaptchouk, JV\n\nVedantam, SL\n\nVerweij, N\n\nVink, JM\n\nVitart, V\n\nWu, Y\n\nYengo, L\n\nZhang, W\n\nHua Zhao, J\n\nZimmermann, ME\n\nZubair, N\n\nAbecasis, GR\n\nAdair, LS\n\nAfaq, S\n\nAfzal, U\n\nBakker, SJL\n\nBartz, TM\n\nBeilby, J\n\nBergman, RN\n\nBergmann, S\n\nBiffar, R\n\nBlangero, J\n\nBoerwinkle, E\n\nBonnycastle, LL\n\nBottinger, E\n\nBraga, D\n\nBuckley, BM\n\nBuyske, S\n\nCampbell, H\n\nChambers, JC\n\nCollins, FS\n\nCurran, JE\n\nde Borst, GJ\n\nde Craen, AJM\n\nde Geus, EJC\n\nDedoussis, G\n\nDelgado, GE\n\nden Ruijter, HM\n\nEiriksdottir, G\n\nEriksson, AL\n\nEsko, T\n\nFaul, JD\n\nFord, I\n\nForrester, T\n\nGertow, K\n\nGigante, B\n\nGlorioso, N\n\nGong, J\n\nGrallert, H\n\nGrammer, TB\n\nGrarup, N\n\nHaitjema, S\n\nHallmans, G\n\nHamsten, A\n\nHansen, T\n\nHarris, TB\n\nHartman, CA\n\nHassinen, M\n\nHastie, ND\n\nHeath, AC\n\nHernandez, D\n\nHindorff, L\n\nHocking, LJ\n\nHollensted, M\n\nHolmen, OL\n\nHomuth, G\n\nJan Hottenga, J\n\nHuang, J\n\nHung, J\n\nHutri-Kähönen, N\n\nIngelsson, E\n\nJames, AL\n\nJansson, JO\n\nJarvelin, MR\n\nJhun, MA\n\nJørgensen, ME\n\nJuonala, M\n\nKähönen, M\n\nKarlsson, M\n\nKoistinen, HA\n\nKolcic, I\n\nKolovou, G\n\nKooperberg, C\n\nKrämer, BK\n\nKuusisto, J\n\nKvaløy, K\n\nLakka, TA\n\nLangenberg, C\n\nLauner, LJ\n\nLeander, K\n\nLee, NR\n\nLind, L\n\nLindgren, CM\n\nLinneberg, A\n\nLobbens, S\n\nLoh, M\n\nLorentzon, M\n\nLuben, R\n\nLubke, G\n\nLudolph-Donislawski, A\n\nLupoli, S\n\nMadden, PAF\n\nMännikkö, R\n\nMarques-Vidal, P\n\nMartin, NG\n\nMcKenzie, CA\n\nMcKnight, B\n\nMellström, D\n\nMenni, C\n\nMontgomery, GW\n\nMusk, AB\n\nNarisu, N\n\nNauck, M\n\nNolte, IM\n\nOldehinkel, AJ\n\nOlden, M\n\nOng, KK\n\nPadmanabhan, S\n\nPeyser, PA\n\nPisinger, C\n\nPorteous, DJ\n\nRaitakari, OT\n\nRankinen, T\n\nRao, DC\n\nRasmussen-Torvik, LJ\n\nRawal, R\n\nRice, T\n\nRidker, PM\n\nRose, LM\n\nBien, SA\n\nRudan, I\n\nSanna, S\n\nSarzynski, MA\n\nSattar, N\n\nSavonen, K\n\nSchlessinger, D\n\nScholtens, S\n\nSchurmann, C\n\nScott, RA\n\nSennblad, B\n\nSiemelink, MA\n\nSilbernagel, G\n\nSlagboom, PE\n\nSnieder, H\n\nStaessen, JA\n\nStott, DJ\n\nSwertz, MA\n\nSwift, AJ\n\nTaylor, KD\n\nTayo, BO\n\nThorand, B\n\nThuillier, D\n\nTuomilehto, J\n\nUitterlinden, AG\n\nVandenput, L\n\nVohl, MC\n\nVölzke, H\n\nVonk, JM\n\nWaeber, G\n\nWaldenberger, M\n\nWestendorp, RGJ\n\nWild, S\n\nWillemsen, G\n\nWolffenbuttel, BHR\n\nWong, A\n\nWright, AF\n\nZhao, W\n\nZillikens, MC\n\nBaldassarre, D\n\nBalkau, B\n\nBandinelli, S\n\nBöger, CA\n\nBoomsma, DI\n\nBouchard, C\n\nBruinenberg, M\n\nChasman, DI\n\nChen, YD\n\nChines, PS\n\nCooper, RS\n\nCucca, F\n\nCusi, D\n\nFaire, U\n\nFerrucci, L\n\nFranks, PW\n\nFroguel, P\n\nGordon-Larsen, P\n\nGrabe, HJ\n\nGudnason, V\n\nHaiman, CA\n\nHayward, C\n\nHveem, K\n\nJohnson, AD\n\nWouter Jukema, J\n\nKardia, SLR\n\nKivimaki, M\n\nKooner, JS\n\nKuh, D\n\nLaakso, M\n\nLehtimäki, T\n\nMarchand, LL\n\nMärz, W\n\nMcCarthy, MI\n\nMetspalu, A\n\nMorris, AP\n\nOhlsson, C\n\nPalmer, LJ\n\nPasterkamp, G\n\nPedersen, O ...\n\nBeiträge in Fachzeitschriften\nISI:000400064600001\n28443625.0\n10.1038/ncomms14977\nPMC5414044\nFew genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51, 80 current smokers and 190, 78 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.\n\nMärz, Winfried\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n155042\nNovel genetic loci underlying human intracranial volume identified through genome-wide association.\n\nAdams, HH\n\nHibar, DP\n\nChouraki, V\n\nStein, JL\n\nNyquist, PA\n\nRentería, ME\n\nTrompet, S\n\nArias-Vasquez, A\n\nSeshadri, S\n\nDesrivières, S\n\nBeecham, AH\n\nJahanshad, N\n\nWittfeld, K\n\nVan der Lee, SJ\n\nAbramovic, L\n\nAlhusaini, S\n\nAmin, N\n\nAndersson, M\n\nArfanakis, K\n\nAribisala, BS\n\nArmstrong, NJ\n\nAthanasiu, L\n\nAxelsson, T\n\nBeiser, A\n\nBernard, M\n\nBis, JC\n\nBlanken, LM\n\nBlanton, SH\n\nBohlken, MM\n\nBoks, MP\n\nBralten, J\n\nBrickman, AM\n\nCarmichael, O\n\nChakravarty, MM\n\nChauhan, G\n\nChen, Q\n\nChing, CR\n\nCuellar-Partida, G\n\nBraber, AD\n\nDoan, NT\n\nEhrlich, S\n\nFilippi, I\n\nGe, T\n\nGiddaluru, S\n\nGoldman, AL\n\nGottesman, RF\n\nGreven, CU\n\nGrimm, O\n\nGriswold, ME\n\nGuadalupe, T\n\nHass, J\n\nHaukvik, UK\n\nHilal, S\n\nHofer, E\n\nHoehn, D\n\nHolmes, AJ\n\nHoogman, M\n\nJanowitz, D\n\nJia, T\n\nKasperaviciute, D\n\nKim, S\n\nKlein, M\n\nKraemer, B\n\nLee, PH\n\nLiao, J\n\nLiewald, DC\n\nLopez, LM\n\nLuciano, M\n\nMacare, C\n\nMarquand, A\n\nMatarin, M\n\nMather, KA\n\nMattheisen, M\n\nMazoyer, B\n\nMcKay, DR\n\nMcWhirter, R\n\nMilaneschi, Y\n\nMirza-Schreiber, N\n\nMuetzel, RL\n\nManiega, SM\n\nNho, K\n\nNugent, AC\n\nLoohuis, LM\n\nOosterlaan, J\n\nPapmeyer, M\n\nPappa, I\n\nPirpamer, L\n\nPudas, S\n\nPütz, B\n\nRajan, KB\n\nRamasamy, A\n\nRichards, JS\n\nRisacher, SL\n\nRoiz-Santiañez, R\n\nRommelse, N\n\nRose, EJ\n\nRoyle, NA\n\nRundek, T\n\nSämann, PG\n\nSatizabal, CL\n\nSchmaal, L\n\nSchork, AJ\n\nShen, L\n\nShin, J\n\nShumskaya, E\n\nSmith, AV\n\nSprooten, E\n\nStrike, LT\n\nTeumer, A\n\nThomson, R\n\nTordesillas-Gutierrez, D\n\nToro, R\n\nTrabzuni, D\n\nVaidya, D\n\nVan der Grond, J\n\nVan der Meer, D\n\nVan Donkelaar, MM\n\nVan Eijk, KR\n\nVan Erp, TG\n\nVan Rooij, D\n\nWalton, E\n\nWestlye, LT\n\nWhelan, CD\n\nWindham, BG\n\nWinkler, AM\n\nWoldehawariat, G\n\nWolf, C\n\nWolfers, T\n\nXu, B\n\nYanek, LR\n\nYang, J\n\nZijdenbos, A\n\nZwiers, MP\n\nAgartz, I\n\nAggarwal, NT\n\nAlmasy, L\n\nAmes, D\n\nAmouyel, P\n\nAndreassen, OA\n\nArepalli, S\n\nAssareh, AA\n\nBarral, S\n\nBastin, ME\n\nBecker, DM\n\nBecker, JT\n\nBennett, DA\n\nBlangero, J\n\nvan Bokhoven, H\n\nBoomsma, DI\n\nBrodaty, H\n\nBrouwer, RM\n\nBrunner, HG\n\nBuckner, RL\n\nBuitelaar, JK\n\nBulayeva, KB\n\nCahn, W\n\nCalhoun, VD\n\nCannon, DM\n\nCavalleri, GL\n\nChen, C\n\nCheng, CY\n\nCichon, S\n\nCookson, MR\n\nCorvin, A\n\nCrespo-Facorro, B\n\nCurran, JE\n\nCzisch, M\n\nDale, AM\n\nDavies, GE\n\nDe Geus, EJ\n\nDe Jager, PL\n\nde Zubicaray, GI\n\nDelanty, N\n\nDepondt, C\n\nDeStefano, AL\n\nDillman, A\n\nDjurovic, S\n\nDonohoe, G\n\nDrevets, WC\n\nDuggirala, R\n\nDyer, TD\n\nErk, S\n\nEspeseth, T\n\nEvans, DA\n\nFedko, IO\n\nFernández, G\n\nFerrucci, L\n\nFisher, SE\n\nFleischman, DA\n\nFord, I\n\nForoud, TM\n\nFox, PT\n\nFrancks, C\n\nFukunaga, M\n\nGibbs, JR\n\nGlahn, DC\n\nGollub, RL\n\nGöring, HH\n\nGrabe, HJ\n\nGreen, RC\n\nGruber, O\n\nGudnason, V\n\nGuelfi, S\n\nHansell, NK\n\nHardy, J\n\nHartman, CA\n\nHashimoto, R\n\nHegenscheid, K\n\nHeinz, A\n\nLe Hellard, S\n\nHernandez, DG\n\nHeslenfeld, DJ\n\nHo, BC\n\nHoekstra, PJ\n\nHoffmann, W\n\nHofman, A\n\nHolsboer, F\n\nHomuth, G\n\nHosten, N\n\nHottenga, JJ\n\nHulshoff Pol, HE\n\nIkeda, M\n\nIkram, MK\n\nJack, CR\n\nJenkinson, M\n\nJohnson, R\n\nJönsson, EG\n\nJukema, JW\n\nKahn, RS\n\nKanai, R\n\nKloszewska, I\n\nKnopman, DS\n\nKochunov, P\n\nKwok, JB\n\nLawrie, SM\n\nLemaître, H\n\nLiu, X\n\nLongo, DL\n\nLongstreth, WT\n\nLopez, OL\n\nLovestone, S\n\nMartinez, O\n\nMartinot, JL\n\nMattay, VS\n\nMcDonald, C\n\nMcIntosh, AM\n\nMcMahon, KL\n\nMcMahon, FJ\n\nMecocci, P\n\nMelle, I\n\nMeyer-Lindenberg, A\n\nMohnke, S\n\nMontgomery, GW\n\nMorris, DW\n\nMosley, TH\n\nMühleisen, TW\n\nMüller-Myhsok, B\n\nNalls, MA\n\nNauck, M\n\nNichols, TE\n\nNiessen, WJ\n\nNöthen, MM\n\nNyberg, L\n\nOhi, K\n\nOlvera, RL\n\nOphoff, RA\n\nPandolfo, M\n\nPaus, T\n\nPausova, Z\n\nPenninx, BW\n\nPike, GB\n\nPotkin, SG\n\nPsaty, BM\n\nReppermund, S\n\nRietschel, M\n\nRoffman, JL\n\nRomanczuk-Seiferth, N\n\nRotter, JI\n\nRyten, M ...\n\nBeiträge in Fachzeitschriften\nISI:000389011900016\n27694991.0\n10.1038/nn.4398\nPMC5227112\nIntracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32, 38 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37, 45). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.\n\nHofer, Edith\n\nPirpamer, Lukas\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n139254\nDefining the role of common variation in the genomic and biological architecture of adult human height.\n\nWood, AR\n\nEsko, T\n\nYang, J\n\nVedantam, S\n\nPers, TH\n\nGustafsson, S\n\nChu, AY\n\nEstrada, K\n\nLuan, J\n\nKutalik, Z\n\nAmin, N\n\nBuchkovich, ML\n\nCroteau-Chonka, DC\n\nDay, FR\n\nDuan, Y\n\nFall, T\n\nFehrmann, R\n\nFerreira, T\n\nJackson, AU\n\nKarjalainen, J\n\nLo, KS\n\nLocke, AE\n\nMägi, R\n\nMihailov, E\n\nPorcu, E\n\nRandall, JC\n\nScherag, A\n\nVinkhuyzen, AA\n\nWestra, HJ\n\nWinkler, TW\n\nWorkalemahu, T\n\nZhao, JH\n\nAbsher, D\n\nAlbrecht, E\n\nAnderson, D\n\nBaron, J\n\nBeekman, M\n\nDemirkan, A\n\nEhret, GB\n\nFeenstra, B\n\nFeitosa, MF\n\nFischer, K\n\nFraser, RM\n\nGoel, A\n\nGong, J\n\nJustice, AE\n\nKanoni, S\n\nKleber, ME\n\nKristiansson, K\n\nLim, U\n\nLotay, V\n\nLui, JC\n\nMangino, M\n\nMateo Leach, I\n\nMedina-Gomez, C\n\nNalls, MA\n\nNyholt, DR\n\nPalmer, CD\n\nPasko, D\n\nPechlivanis, S\n\nProkopenko, I\n\nRied, JS\n\nRipke, S\n\nShungin, D\n\nStancáková, A\n\nStrawbridge, RJ\n\nSung, YJ\n\nTanaka, T\n\nTeumer, A\n\nTrompet, S\n\nvan der Laan, SW\n\nvan Setten, J\n\nVan Vliet-Ostaptchouk, JV\n\nWang, Z\n\nYengo, L\n\nZhang, W\n\nAfzal, U\n\nArnlöv, J\n\nArscott, GM\n\nBandinelli, S\n\nBarrett, A\n\nBellis, C\n\nBennett, AJ\n\nBerne, C\n\nBlüher, M\n\nBolton, JL\n\nBöttcher, Y\n\nBoyd, HA\n\nBruinenberg, M\n\nBuckley, BM\n\nBuyske, S\n\nCaspersen, IH\n\nChines, PS\n\nClarke, R\n\nClaudi-Boehm, S\n\nCooper, M\n\nDaw, EW\n\nDe Jong, PA\n\nDeelen, J\n\nDelgado, G\n\nDenny, JC\n\nDhonukshe-Rutten, R\n\nDimitriou, M\n\nDoney, AS\n\nDörr, M\n\nEklund, N\n\nEury, E\n\nFolkersen, L\n\nGarcia, ME\n\nGeller, F\n\nGiedraitis, V\n\nGo, AS\n\nGrallert, H\n\nGrammer, TB\n\nGräßler, J\n\nGrönberg, H\n\nde Groot, LC\n\nGroves, CJ\n\nHaessler, J\n\nHall, P\n\nHaller, T\n\nHallmans, G\n\nHannemann, A\n\nHartman, CA\n\nHassinen, M\n\nHayward, C\n\nHeard-Costa, NL\n\nHelmer, Q\n\nHemani, G\n\nHenders, AK\n\nHillege, HL\n\nHlatky, MA\n\nHoffmann, W\n\nHoffmann, P\n\nHolmen, O\n\nHouwing-Duistermaat, JJ\n\nIllig, T\n\nIsaacs, A\n\nJames, AL\n\nJeff, J\n\nJohansen, B\n\nJohansson, Å\n\nJolley, J\n\nJuliusdottir, T\n\nJunttila, J\n\nKho, AN\n\nKinnunen, L\n\nKlopp, N\n\nKocher, T\n\nKratzer, W\n\nLichtner, P\n\nLind, L\n\nLindström, J\n\nLobbens, S\n\nLorentzon, M\n\nLu, Y\n\nLyssenko, V\n\nMagnusson, PK\n\nMahajan, A\n\nMaillard, M\n\nMcArdle, WL\n\nMcKenzie, CA\n\nMcLachlan, S\n\nMcLaren, PJ\n\nMenni, C\n\nMerger, S\n\nMilani, L\n\nMoayyeri, A\n\nMonda, KL\n\nMorken, MA\n\nMüller, G\n\nMüller-Nurasyid, M\n\nMusk, AW\n\nNarisu, N\n\nNauck, M\n\nNolte, IM\n\nNöthen, MM\n\nOozageer, L\n\nPilz, S\n\nRayner, NW\n\nRenstrom, F\n\nRobertson, NR\n\nRose, LM\n\nRoussel, R\n\nSanna, S\n\nScharnagl, H\n\nScholtens, S\n\nSchumacher, FR\n\nSchunkert, H\n\nScott, RA\n\nSehmi, J\n\nSeufferlein, T\n\nShi, J\n\nSilventoinen, K\n\nSmit, JH\n\nSmith, AV\n\nSmolonska, J\n\nStanton, AV\n\nStirrups, K\n\nStott, DJ\n\nStringham, HM\n\nSundström, J\n\nSwertz, MA\n\nSyvänen, AC\n\nTayo, BO\n\nThorleifsson, G\n\nTyrer, JP\n\nvan Dijk, S\n\nvan Schoor, NM\n\nvan der Velde, N\n\nvan Heemst, D\n\nvan Oort, FV\n\nVermeulen, SH\n\nVerweij, N\n\nVonk, JM\n\nWaite, LL\n\nWaldenberger, M\n\nWennauer, R\n\nWilkens, LR\n\nWillenborg, C\n\nWilsgaard, T\n\nWojczynski, MK\n\nWong, A\n\nWright, AF\n\nZhang, Q\n\nArveiler, D\n\nBakker, SJ\n\nBeilby, J\n\nBergman, RN\n\nBergmann, S\n\nBiffar, R\n\nBlangero, J\n\nBoomsma, DI\n\nBornstein, SR\n\nBovet, P\n\nBrambilla, P\n\nBrown, MJ\n\nCampbell, H\n\nCaulfield, MJ\n\nChakravarti, A\n\nCollins, R\n\nCollins, FS\n\nCrawford, DC\n\nCupples, LA\n\nDanesh, J\n\nde Faire, U\n\nden Ruijter, HM\n\nErbel, R\n\nErdmann, J\n\nEriksson, JG\n\nFarrall, M\n\nFerrannini, E\n\nFerrières, J\n\nFord, I\n\nForouhi, NG\n\nForrester, T\n\nGansevoort, RT\n\nGejman, PV\n\nGieger, C\n\nGolay, A\n\nGottesman, O\n\nGudnason, V\n\nGyllensten, U\n\nHaas, DW\n\nHall, AS\n\nHarris, TB\n\nHattersley, AT\n\nHeath, AC\n\nHengstenberg, C\n\nHicks, AA\n\nHindorff, LA\n\nHingorani, AD\n\nHofman, A\n\nHovingh, GK\n\nHumphries, SE\n\nHunt, SC\n\nHypponen, E\n\nJacobs, KB\n\nJarvelin, MR\n\nJousilahti, P ...\n\nBeiträge in Fachzeitschriften\nISI:000344131900008\n25282103.0\n10.1038/ng.3097\nPMC4250049\nUsing genome-wide data from 253, 88 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2, 00, ∼3, 00 and ∼9, 00 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.\n\nMärz, Winfried\n\nPilz, Stefan\n\nScharnagl, Hubert\n\n\n"
},
{
"text": "\n165103\nGenome-wide physical activity interactions in adiposity - A meta-analysis of 200,452 adults.\n\nGraff, M\n\nScott, RA\n\nJustice, AE\n\nYoung, KL\n\nFeitosa, MF\n\nBarata, L\n\nWinkler, TW\n\nChu, AY\n\nMahajan, A\n\nHadley, D\n\nXue, L\n\nWorkalemahu, T\n\nHeard-Costa, NL\n\nden Hoed, M\n\nAhluwalia, TS\n\nQi, Q\n\nNgwa, JS\n\nRenström, F\n\nQuaye, L\n\nEicher, JD\n\nHayes, JE\n\nCornelis, M\n\nKutalik, Z\n\nLim, E\n\nLuan, J\n\nHuffman, JE\n\nZhang, W\n\nZhao, W\n\nGriffin, PJ\n\nHaller, T\n\nAhmad, S\n\nMarques-Vidal, PM\n\nBien, S\n\nYengo, L\n\nTeumer, A\n\nSmith, AV\n\nKumari, M\n\nHarder, MN\n\nJustesen, JM\n\nKleber, ME\n\nHollensted, M\n\nLohman, K\n\nRivera, NV\n\nWhitfield, JB\n\nZhao, JH\n\nStringham, HM\n\nLyytikäinen, LP\n\nHuppertz, C\n\nWillemsen, G\n\nPeyrot, WJ\n\nWu, Y\n\nKristiansson, K\n\nDemirkan, A\n\nFornage, M\n\nHassinen, M\n\nBielak, LF\n\nCadby, G\n\nTanaka, T\n\nMägi, R\n\nvan der Most, PJ\n\nJackson, AU\n\nBragg-Gresham, JL\n\nVitart, V\n\nMarten, J\n\nNavarro, P\n\nBellis, C\n\nPasko, D\n\nJohansson, Å\n\nSnitker, S\n\nCheng, YC\n\nEriksson, J\n\nLim, U\n\nAadahl, M\n\nAdair, LS\n\nAmin, N\n\nBalkau, B\n\nAuvinen, J\n\nBeilby, J\n\nBergman, RN\n\nBergmann, S\n\nBertoni, AG\n\nBlangero, J\n\nBonnefond, A\n\nBonnycastle, LL\n\nBorja, JB\n\nBrage, S\n\nBusonero, F\n\nBuyske, S\n\nCampbell, H\n\nChines, PS\n\nCollins, FS\n\nCorre, T\n\nSmith, GD\n\nDelgado, GE\n\nDueker, N\n\nDörr, M\n\nEbeling, T\n\nEiriksdottir, G\n\nEsko, T\n\nFaul, JD\n\nFu, M\n\nFærch, K\n\nGieger, C\n\nGläser, S\n\nGong, J\n\nGordon-Larsen, P\n\nGrallert, H\n\nGrammer, TB\n\nGrarup, N\n\nvan Grootheest, G\n\nHarald, K\n\nHastie, ND\n\nHavulinna, AS\n\nHernandez, D\n\nHindorff, L\n\nHocking, LJ\n\nHolmens, OL\n\nHolzapfel, C\n\nHottenga, JJ\n\nHuang, J\n\nHuang, T\n\nHui, J\n\nHuth, C\n\nHutri-Kähönen, N\n\nJames, AL\n\nJansson, JO\n\nJhun, MA\n\nJuonala, M\n\nKinnunen, L\n\nKoistinen, HA\n\nKolcic, I\n\nKomulainen, P\n\nKuusisto, J\n\nKvaløy, K\n\nKähönen, M\n\nLakka, TA\n\nLauner, LJ\n\nLehne, B\n\nLindgren, CM\n\nLorentzon, M\n\nLuben, R\n\nMarre, M\n\nMilaneschi, Y\n\nMonda, KL\n\nMontgomery, GW\n\nDe Moor, MHM\n\nMulas, A\n\nMüller-Nurasyid, M\n\nMusk, AW\n\nMännikkö, R\n\nMännistö, S\n\nNarisu, N\n\nNauck, M\n\nNettleton, JA\n\nNolte, IM\n\nOldehinkel, AJ\n\nOlden, M\n\nOng, KK\n\nPadmanabhan, S\n\nPaternoster, L\n\nPerez, J\n\nPerola, M\n\nPeters, A\n\nPeters, U\n\nPeyser, PA\n\nProkopenko, I\n\nPuolijoki, H\n\nRaitakari, OT\n\nRankinen, T\n\nRasmussen-Torvik, LJ\n\nRawal, R\n\nRidker, PM\n\nRose, LM\n\nRudan, I\n\nSarti, C\n\nSarzynski, MA\n\nSavonen, K\n\nScott, WR\n\nSanna, S\n\nShuldiner, AR\n\nSidney, S\n\nSilbernagel, G\n\nSmith, BH\n\nSmith, JA\n\nSnieder, H\n\nStančáková, A\n\nSternfeld, B\n\nSwift, AJ\n\nTammelin, T\n\nTan, ST\n\nThorand, B\n\nThuillier, D\n\nVandenput, L\n\nVestergaard, H\n\nvan Vliet-Ostaptchouk, JV\n\nVohl, MC\n\nVölker, U\n\nWaeber, G\n\nWalker, M\n\nWild, S\n\nWong, A\n\nWright, AF\n\nZillikens, MC\n\nZubair, N\n\nHaiman, CA\n\nLemarchand, L\n\nGyllensten, U\n\nOhlsson, C\n\nHofman, A\n\nRivadeneira, F\n\nUitterlinden, AG\n\nPérusse, L\n\nWilson, JF\n\nHayward, C\n\nPolasek, O\n\nCucca, F\n\nHveem, K\n\nHartman, CA\n\nTönjes, A\n\nBandinelli, S\n\nPalmer, LJ\n\nKardia, SLR\n\nRauramaa, R\n\nSørensen, TIA\n\nTuomilehto, J\n\nSalomaa, V\n\nPenninx, BWJH\n\nde Geus, EJC\n\nBoomsma, DI\n\nLehtimäki, T\n\nMangino, M\n\nLaakso, M\n\nBouchard, C\n\nMartin, NG\n\nKuh, D\n\nLiu, Y\n\nLinneberg, A\n\nMärz, W\n\nStrauch, K\n\nKivimäki, M\n\nHarris, TB\n\nGudnason, V\n\nVölzke, H\n\nQi, L\n\nJärvelin, MR\n\nChambers, JC\n\nKooner, JS\n\nFroguel, P\n\nKooperberg, C\n\nVollenweider, P\n\nHallmans, G\n\nHansen, T\n\nPedersen, O\n\nMetspalu, A\n\nWareham, NJ\n\nLangenberg, C\n\nWeir, DR\n\nPorteous, DJ\n\nBoerwinkle, E\n\nChasman, DI\n\nCHARGE Consortium\n\nEPIC-InterAct Consortium\n\nPAGE Consortium\n\nAbecasis, GR\n\nBarroso, I\n\nMcCarthy, MI\n\nFrayling, TM\n\nO'Connell, JR\n\nvan Duijn, CM\n\nBoehnke, M\n\nHeid, IM\n\nMohlke, KL\n\nStrachan, DP\n\nFox, CS\n\nLiu, CT\n\nHirschhorn, JN\n\nKlein, RJ\n\nJohnson, AD\n\nBorecki, IB\n\nFranks, PW\n\nNorth, KE\n\nC\n\nBeiträge in Fachzeitschriften\nISI:000402549200002\n28448500.0\n10.1371/journal.pgen.1006528\nPMC5407576\nPhysical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200, 52 adults of European (n = 180, 23) or other ancestry (n = 20, 29). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.\n\nMärz, Winfried\n\nSilbernagel, Günther\n\n\n"
},
{
"text": "\n65919\nRationale and design of the LURIC study--a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease.\n\nWinkelmann, BR\n\nMärz, W\n\nBoehm, BO\n\nZotz, R\n\nHager, J\n\nHellstern, P\n\nSenges, J\n\nLURIC Study Group (LUdwigshafen RIsk and Cardiovascular Health)\n\nBeiträge in Fachzeitschriften\nISI:000173541000001\n11258203.0\nNone\nNone\nBACKGROUND AND AIM: Coronary artery disease (CAD), arterial hypertension and Type 2 diabetes mellitus are common polygenetic disorders which have a major impact on public health. Disease prevalence and progression to cardiovascular complications, such as myocardial infarction (MI), stroke or heart failure, are the product of environment and gene interaction. The LUdwigshafen RIsk and Cardiovascular Health (LURIC) study aims to provide a well-defined resource for the study of environmental and genetic risk factors, and their interactions, and the study of functional relationships between gene variation and biochemical phenotype (functional genomics) or response to medication (pharmacogenomics). Long-term follow-up on clinical events will allow us to study the prognostic importance of common genetic variants (polymorphisms) and plasma biomarkers. SETTING: Cardiology unit in tertiary care medical centre in south-west Germany. STUDY DESIGN: Prospective cohort study of individuals with and without cardiovascular disease at baseline. PATIENTS AND METHODS: LURIC is an ongoing prospective study of currently > 3300 individuals in whom the cardiovascular and metabolic phenotypes CAD, MI, dyslipidaemia, hypertension, metabolic syndrome and diabetes mellitus have been defined or ruled out using standardised methodologies in all study participants. Inclusion criteria for LURIC were: German ancestry (limitation of genetic heterogeneity) clinical stability (except for acute coronary syndromes [ACSs]) availability of a coronary angiogram (this inclusion criterium was waived for family members provided that they met all other inclusion and exclusion criteria) Exclusion criteria were: any acute illness other than ACSs any chronic disease where non-cardiac disease predominated a history of malignancy within the past five years. Exclusion criteria were pre-specified in order to minimise the impact of concomitant non-cardiovascular disease on intermediate biochemical phenotypes or on clinical prognosis (limitation of clinical heterogeneity). A standardised personal and family history questionnaire and an extensive laboratory work-up (including glucose tolerance testing in non-diabetics and objective assessment of smoking exposure by determination of cotinine plasma levels) was obtained from all individuals after informed consent. A total of 115 ml of fasting venous blood was sampled for the determination of a pre-specified wide range of intermediate biochemical phenotypes in serum, plasma or whole blood, for leukocyte DNA extraction and immortalisation of B-lymphocytes. Biochemical phenotypes measured included markers of endothelial dysfunction, inflammation, oxidative status, coagulation, lipid metabolism and flow cytometric surface receptor expression of lympho-, mono- and thrombocytes. In addition, multiple aliquots of blood samples were stored for future analyses. RESULTS: A total of 3500 LURIC baseline measurements were performed in 3316 individuals between July 1997 and January 2000. The baseline examination was repeated within a median of 35 days in 5% of study participants (n = 166, including a third examination in 18 after a median of 69 days) for pharmacogenomic assessment of lipid-lowering therapy and for quality control purposes. A five-year follow-up on major clinical events (death, any cardiovascular event including MI, stroke and revascularisation, malignancy and any hospitalisation) is ongoing. The clinical phenotypes prevalent at baseline in the cohort of 2309 men (70%) with a mean age of 62 +/- 11 years and 1007 women (30%), mean age 65 +/- 10 years, were angiographically-documented CAD in 2567 (79%), MI in 1368 (41%), dyslipidaemia in 2050 (62%) with hypercholesterolaemia > or = 240 mg/dl (27%), hypertriglyceridaemia > or = 150 mg/dl (44%) and HDL-cholesterol < or = 35 mg/dl (38%) in individuals not treated with lipid-lowering agents, systemic hypertension in 1921 (58%), metabolic syndrome in 1591 (48%), Type 2 diabetes in 1063 (32%) and obesity defined by body mass index > or = 30 kg/m2 in 770 (23%). Control patients in whom CAD had been ruled out angiographically were five years younger than those with CAD (59 +/- 12 and 64 +/- 10 years, respectively; p < 0.001), twice as often females (48% compared to 25% females in the CAD group, p < 0.001) and had significantly less cardiovascular risk factors than individuals with CAD. The prevalence of specific cardiovascular risk subsets in LURIC, such as the elderly (> or = 75 years), was 375 (11%), while 213 (6%) were young adults (< 45 years) and 904 (27%) were postmenopausal women (90% of all females). A low risk status (< or = 1 out of the four traditional risk factors: dyslipidaemia, smoking, hypertension and diabetes mellitus) was identified in 314 (9%) individuals of the entire cohort (5% in CAD and 26% in controls, p < 0.001) and 97 (3%) carried none of the four risk factors (1% in CAD and 9% in controls, p < 0.001). (ABSTRACT TRUNCATED)\n\nMärz, Winfried\n\n\n"
},
{
"text": "\n178008\nAssociations of autozygosity with a broad range of human phenotypes.\n\nClark, DW\n\nOkada, Y\n\nMoore, KHS\n\nMason, D\n\nPirastu, N\n\nGandin, I\n\nMattsson, H\n\nBarnes, CLK\n\nLin, K\n\nZhao, JH\n\nDeelen, P\n\nRohde, R\n\nSchurmann, C\n\nGuo, X\n\nGiulianini, F\n\nZhang, W\n\nMedina-Gomez, C\n\nKarlsson, R\n\nBao, Y\n\nBartz, TM\n\nBaumbach, C\n\nBiino, G\n\nBixley, MJ\n\nBrumat, M\n\nChai, JF\n\nCorre, T\n\nCousminer, DL\n\nDekker, AM\n\nEccles, DA\n\nvan Eijk, KR\n\nFuchsberger, C\n\nGao, H\n\nGermain, M\n\nGordon, SD\n\nde Haan, HG\n\nHarris, SE\n\nHofer, E\n\nHuerta-Chagoya, A\n\nIgartua, C\n\nJansen, IE\n\nJia, Y\n\nKacprowski, T\n\nKarlsson, T\n\nKleber, ME\n\nLi, SA\n\nLi-Gao, R\n\nMahajan, A\n\nMatsuda, K\n\nMeidtner, K\n\nMeng, W\n\nMontasser, ME\n\nvan der Most, PJ\n\nMunz, M\n\nNutile, T\n\nPalviainen, T\n\nPrasad, G\n\nPrasad, RB\n\nPriyanka, TDS\n\nRizzi, F\n\nSalvi, E\n\nSapkota, BR\n\nShriner, D\n\nSkotte, L\n\nSmart, MC\n\nSmith, AV\n\nvan der Spek, A\n\nSpracklen, CN\n\nStrawbridge, RJ\n\nTajuddin, SM\n\nTrompet, S\n\nTurman, C\n\nVerweij, N\n\nViberti, C\n\nWang, L\n\nWarren, HR\n\nWootton, RE\n\nYanek, LR\n\nYao, J\n\nYousri, NA\n\nZhao, W\n\nAdeyemo, AA\n\nAfaq, S\n\nAguilar-Salinas, CA\n\nAkiyama, M\n\nAlbert, ML\n\nAllison, MA\n\nAlver, M\n\nAung, T\n\nAzizi, F\n\nBentley, AR\n\nBoeing, H\n\nBoerwinkle, E\n\nBorja, JB\n\nde Borst, GJ\n\nBottinger, EP\n\nBroer, L\n\nCampbell, H\n\nChanock, S\n\nChee, ML\n\nChen, G\n\nChen, YI\n\nChen, Z\n\nChiu, YF\n\nCocca, M\n\nCollins, FS\n\nConcas, MP\n\nCorley, J\n\nCugliari, G\n\nvan Dam, RM\n\nDamulina, A\n\nDaneshpour, MS\n\nDay, FR\n\nDelgado, GE\n\nDhana, K\n\nDoney, ASF\n\nDörr, M\n\nDoumatey, AP\n\nDzimiri, N\n\nEbenesersdóttir, SS\n\nElliott, J\n\nElliott, P\n\nEwert, R\n\nFelix, JF\n\nFischer, K\n\nFreedman, BI\n\nGirotto, G\n\nGoel, A\n\nGögele, M\n\nGoodarzi, MO\n\nGraff, M\n\nGranot-Hershkovitz, E\n\nGrodstein, F\n\nGuarrera, S\n\nGudbjartsson, DF\n\nGuity, K\n\nGunnarsson, B\n\nGuo, Y\n\nHagenaars, SP\n\nHaiman, CA\n\nHalevy, A\n\nHarris, TB\n\nHedayati, M\n\nvan Heel, DA\n\nHirata, M\n\nHöfer, I\n\nHsiung, CA\n\nHuang, J\n\nHung, YJ\n\nIkram, MA\n\nJagadeesan, A\n\nJousilahti, P\n\nKamatani, Y\n\nKanai, M\n\nKerrison, ND\n\nKessler, T\n\nKhaw, KT\n\nKhor, CC\n\nde Kleijn, DPV\n\nKoh, WP\n\nKolcic, I\n\nKraft, P\n\nKrämer, BK\n\nKutalik, Z\n\nKuusisto, J\n\nLangenberg, C\n\nLauner, LJ\n\nLawlor, DA\n\nLee, IT\n\nLee, WJ\n\nLerch, MM\n\nLi, L\n\nLiu, J\n\nLoh, M\n\nLondon, SJ\n\nLoomis, S\n\nLu, Y\n\nLuan, J\n\nMägi, R\n\nManichaikul, AW\n\nManunta, P\n\nMásson, G\n\nMatoba, N\n\nMei, XW\n\nMeisinger, C\n\nMeitinger, T\n\nMezzavilla, M\n\nMilani, L\n\nMillwood, IY\n\nMomozawa, Y\n\nMoore, A\n\nMorange, PE\n\nMoreno-Macías, H\n\nMori, TA\n\nMorrison, AC\n\nMuka, T\n\nMurakami, Y\n\nMurray, AD\n\nde Mutsert, R\n\nMychaleckyj, JC\n\nNalls, MA\n\nNauck, M\n\nNeville, MJ\n\nNolte, IM\n\nOng, KK\n\nOrozco, L\n\nPadmanabhan, S\n\nPálsson, G\n\nPankow, JS\n\nPattaro, C\n\nPattie, A\n\nPolasek, O\n\nPoulter, N\n\nPramstaller, PP\n\nQuintana-Murci, L\n\nRäikkönen, K\n\nRalhan, S\n\nRao, DC\n\nvan Rheenen, W\n\nRich, SS\n\nRidker, PM\n\nRietveld, CA\n\nRobino, A\n\nvan Rooij, FJA\n\nRuggiero, D\n\nSaba, Y\n\nSabanayagam, C\n\nSabater-Lleal, M\n\nSala, CF\n\nSalomaa, V\n\nSandow, K\n\nSchmidt, H\n\nScott, LJ\n\nScott, WR\n\nSedaghati-Khayat, B\n\nSennblad, B\n\nvan Setten, J\n\nSever, PJ\n\nSheu, WH\n\nShi, Y\n\nShrestha, S\n\nShukla, SR\n\nSigurdsson, JK\n\nSikka, TT\n\nSingh, JR\n\nSmith, BH\n\nStančáková, A\n\nStanton, A\n\nStarr, JM\n\nStefansdottir, L\n\nStraker, L\n\nSulem, P\n\nSveinbjornsson, G\n\nSwertz, MA\n\nTaylor, AM\n\nTaylor, KD\n\nTerzikhan, N\n\nTham, YC\n\nThorleifsson, G\n\nThorsteinsdottir, U\n\nTillander, A\n\nTracy, RP\n\nTusié-Luna, T\n\nTzoulaki, I\n\nVaccargiu, S\n\nVangipurapu, J\n\nVeldink, JH\n\nVitart, V\n\nVölker, U\n\nVuoksimaa, E\n\nWakil, SM\n\nWaldenberger, M\n\nWander, GS\n\nWang, YX\n\nWareham, NJ\n\nWild, S\n\nYajnik, CS\n\nYuan, JM\n\nZeng, L\n\nZhang, L\n\nZhou, J\n\nAmin, N\n\nAsselbergs, FW\n\nBakker, SJL\n\nBecker, DM\n\nLehne, B\n\nBennett, DA\n\nvan den Berg, L ...\n\nBeiträge in Fachzeitschriften\nISI:000493438700005\n31673082.0\n10.1038/s41467-019-12283-6\nPMC6823371\nIn many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.\n\nDamulina, Anna\n\nHofer, Edith\n\nMärz, Winfried\n\nSABA, Yasaman\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n185315\nLong-term effects of weight-reducing drugs in people with hypertension.\n\nSiebenhofer, A\n\nWinterholer, S\n\nJeitler, K\n\nHorvath, K\n\nBerghold, A\n\nKrenn, C\n\nSemlitsch, T\n\nBeiträge in Fachzeitschriften\nISI:000613501500025\n33454957.0\n10.1002/14651858.CD007654.pub5\nNone\nThis is the third update of this review, first published in July 2009. All major guidelines on treatment of hypertension recommend weight loss; anti-obesity drugs may be able to help in this respect.\n Primary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events).. Secondary objectives: To assess the long-term effects of pharmacologically-induced reduction in body weight in adults with essential hypertension on change from baseline in systolic and diastolic blood pressure, and on body weight reduction.\n For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. The searches had no language restrictions. We contacted authors of relevant papers about further published and unpublished work.\n Randomised controlled trials of at least 24 weeks' duration in adults with hypertension that compared approved long-term weight-loss medications to placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, assessed risks of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using a fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of the heterogeneity.\n This third update of the review added one new trial, investigating the combination of naltrexone/bupropion versus placebo. Two medications, which were included in the previous versions of this review (rimonabant and sibutramine) are no longer considered relevant for this update, since their marketing approval was withdrawn in 2010 and 2009, respectively. The number of included studies in this review update is therefore six (12, 24 participants in total): four RCTs comparing orlistat to placebo, involving a total of 3132 participants with high blood pressure and a mean age of 46 to 55 years; one trial comparing phentermine/topiramate to placebo, involving 1305 participants with high blood pressure and a mean age of 53 years; and one trial comparing naltrexone/bupropion to placebo, involving 8283 participants with hypertension and a mean age of 62 years. We judged the risks of bias to be unclear for the trials investigating orlistat or naltrexone/bupropion. and low for the trial investigating phentermine/topiramate. Only the study of naltrexone/bupropion included cardiovascular mortality and morbidity as predefined outcomes. There were no differences in the rates of all-cause or cardiovascular mortality, major cardiovascular events, or serious adverse events between naltrexone/bupropion and placebo. The incidence of overall adverse events was significantly higher in participants treated with naltrexone/bupropion. For orlistat, the incidence of gastrointestinal side effects was consistently higher compared to placebo. The most frequent side effects with phentermine/topiramate were dry mouth and paraesthesia. After six to 12 months, orlistat reduced systolic blood pressure compared to placebo by mean difference (MD) -2.6 mm Hg (95% confidence interval (CI) -3.8 to -1.4 mm Hg; 4 trials, 2058 participants) and diastolic blood pressure by MD -2.0 mm Hg (95% CI -2.7 to -1.2 mm Hg; 4 trials, 2058 participants). After 13 months of follow-up, phentermine/topiramate decreased systolic blood pressure compared to placebo by -2.0 to -4.2 mm Hg (1 trial, 1030 participants) (depending on drug dosage), and diastolic blood pressure by -1.3 to -1.9 mm Hg (1 trial, 1030 participants) (depending on drug dosage). There was no difference in the change in systolic or diastolic blood pressure between naltrexone/bupropion and placebo (1 trial, 8283 participants). We identified no relevant studies investigating liraglutide or lorcaserin in people with hypertension.\n In people with elevated blood pressure, orlistat, phentermine/topiramate and naltrexone/bupropion reduced body weight; the magnitude of the effect was greatest with phentermine/topiramate. In the same trials, orlistat and phentermine/topiramate, but not naltrexone/bupropion, reduced blood pressure. One RCT of naltrexone/bupropion versus placebo showed no differences in all-cause mortality or cardiovascular mortality or morbidity after two years. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while for lorcaserin the application for European marketing authorisation was withdrawn due to a negative overall benefit/risk balance. In 2020 lorcaserin was also withdrawn from the US market. Two other medications (rimonabant and sibutramine) had already been withdrawn from the market in 2009 and 2010, respectively.\n Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.\n\nBerghold, Andrea\n\nHorvath, Karl\n\nJeitler, Klaus\n\nKrenn, Cornelia\n\nSemlitsch, Thomas\n\nSiebenhofer-Kroitzsch, Andrea\n\n\n"
},
{
"text": "\n175392\nA catalog of genetic loci associated with kidney function from analyses of a million individuals.\n\nWuttke, M\n\nLi, Y\n\nLi, M\n\nSieber, KB\n\nFeitosa, MF\n\nGorski, M\n\nTin, A\n\nWang, L\n\nChu, AY\n\nHoppmann, A\n\nKirsten, H\n\nGiri, A\n\nChai, JF\n\nSveinbjornsson, G\n\nTayo, BO\n\nNutile, T\n\nFuchsberger, C\n\nMarten, J\n\nCocca, M\n\nGhasemi, S\n\nXu, Y\n\nHorn, K\n\nNoce, D\n\nvan der Most, PJ\n\nSedaghat, S\n\nYu, Z\n\nAkiyama, M\n\nAfaq, S\n\nAhluwalia, TS\n\nAlmgren, P\n\nAmin, N\n\nÄrnlöv, J\n\nBakker, SJL\n\nBansal, N\n\nBaptista, D\n\nBergmann, S\n\nBiggs, ML\n\nBiino, G\n\nBoehnke, M\n\nBoerwinkle, E\n\nBoissel, M\n\nBottinger, EP\n\nBoutin, TS\n\nBrenner, H\n\nBrumat, M\n\nBurkhardt, R\n\nButterworth, AS\n\nCampana, E\n\nCampbell, A\n\nCampbell, H\n\nCanouil, M\n\nCarroll, RJ\n\nCatamo, E\n\nChambers, JC\n\nChee, ML\n\nChee, ML\n\nChen, X\n\nCheng, CY\n\nCheng, Y\n\nChristensen, K\n\nCifkova, R\n\nCiullo, M\n\nConcas, MP\n\nCook, JP\n\nCoresh, J\n\nCorre, T\n\nSala, CF\n\nCusi, D\n\nDanesh, J\n\nDaw, EW\n\nde Borst, MH\n\nDe Grandi, A\n\nde Mutsert, R\n\nde Vries, APJ\n\nDegenhardt, F\n\nDelgado, G\n\nDemirkan, A\n\nDi Angelantonio, E\n\nDittrich, K\n\nDivers, J\n\nDorajoo, R\n\nEckardt, KU\n\nEhret, G\n\nElliott, P\n\nEndlich, K\n\nEvans, MK\n\nFelix, JF\n\nFoo, VHX\n\nFranco, OH\n\nFranke, A\n\nFreedman, BI\n\nFreitag-Wolf, S\n\nFriedlander, Y\n\nFroguel, P\n\nGansevoort, RT\n\nGao, H\n\nGasparini, P\n\nGaziano, JM\n\nGiedraitis, V\n\nGieger, C\n\nGirotto, G\n\nGiulianini, F\n\nGögele, M\n\nGordon, SD\n\nGudbjartsson, DF\n\nGudnason, V\n\nHaller, T\n\nHamet, P\n\nHarris, TB\n\nHartman, CA\n\nHayward, C\n\nHellwege, JN\n\nHeng, CK\n\nHicks, AA\n\nHofer, E\n\nHuang, W\n\nHutri-Kähönen, N\n\nHwang, SJ\n\nIkram, MA\n\nIndridason, OS\n\nIngelsson, E\n\nIsing, M\n\nJaddoe, VWV\n\nJakobsdottir, J\n\nJonas, JB\n\nJoshi, PK\n\nJosyula, NS\n\nJung, B\n\nKähönen, M\n\nKamatani, Y\n\nKammerer, CM\n\nKanai, M\n\nKastarinen, M\n\nKerr, SM\n\nKhor, CC\n\nKiess, W\n\nKleber, ME\n\nKoenig, W\n\nKooner, JS\n\nKörner, A\n\nKovacs, P\n\nKraja, AT\n\nKrajcoviechova, A\n\nKramer, H\n\nKrämer, BK\n\nKronenberg, F\n\nKubo, M\n\nKühnel, B\n\nKuokkanen, M\n\nKuusisto, J\n\nLa Bianca, M\n\nLaakso, M\n\nLange, LA\n\nLangefeld, CD\n\nLee, JJ\n\nLehne, B\n\nLehtimäki, T\n\nLieb, W\n\nLifelines Cohort Study\n\nLim, SC\n\nLind, L\n\nLindgren, CM\n\nLiu, J\n\nLiu, J\n\nLoeffler, M\n\nLoos, RJF\n\nLucae, S\n\nLukas, MA\n\nLyytikäinen, LP\n\nMägi, R\n\nMagnusson, PKE\n\nMahajan, A\n\nMartin, NG\n\nMartins, J\n\nMärz, W\n\nMascalzoni, D\n\nMatsuda, K\n\nMeisinger, C\n\nMeitinger, T\n\nMelander, O\n\nMetspalu, A\n\nMikaelsdottir, EK\n\nMilaneschi, Y\n\nMiliku, K\n\nMishra, PP\n\nV. A. Million Veteran Program\n\nMohlke, KL\n\nMononen, N\n\nMontgomery, GW\n\nMook-Kanamori, DO\n\nMychaleckyj, JC\n\nNadkarni, GN\n\nNalls, MA\n\nNauck, M\n\nNikus, K\n\nNing, B\n\nNolte, IM\n\nNoordam, R\n\nO'Connell, J\n\nO'Donoghue, ML\n\nOlafsson, I\n\nOldehinkel, AJ\n\nOrho-Melander, M\n\nOuwehand, WH\n\nPadmanabhan, S\n\nPalmer, ND\n\nPalsson, R\n\nPenninx, BWJH\n\nPerls, T\n\nPerola, M\n\nPirastu, M\n\nPirastu, N\n\nPistis, G\n\nPodgornaia, AI\n\nPolasek, O\n\nPonte, B\n\nPorteous, DJ\n\nPoulain, T\n\nPramstaller, PP\n\nPreuss, MH\n\nPrins, BP\n\nProvince, MA\n\nRabelink, TJ\n\nRaffield, LM\n\nRaitakari, OT\n\nReilly, DF\n\nRettig, R\n\nRheinberger, M\n\nRice, KM\n\nRidker, PM\n\nRivadeneira, F\n\nRizzi, F\n\nRoberts, DJ\n\nRobino, A\n\nRossing, P\n\nRudan, I\n\nRueedi, R\n\nRuggiero, D\n\nRyan, KA\n\nSaba, Y\n\nSabanayagam, C\n\nSalomaa, V\n\nSalvi, E\n\nSaum, KU\n\nSchmidt, H\n\nSchmidt, R\n\nSchöttker, B\n\nSchulz, CA\n\nSchupf, N\n\nShaffer, CM\n\nShi, Y\n\nSmith, AV\n\nSmith, BH\n\nSoranzo, N\n\nSpracklen, CN\n\nStrauch, K\n\nStringham, HM\n\nStumvoll, M\n\nSvensson, PO\n\nSzymczak, S\n\nTai, ES\n\nTajuddin, SM\n\nTan, NYQ\n\nTaylor, KD\n\nTeren, A\n\nTham, YC\n\nThiery, J\n\nThio, CHL\n\nThomsen, H\n\nThorleifsson, G\n\nToniolo, D\n\nTönjes, A\n\nTremblay, J\n\nTzoulaki, I\n\nUitterlinden, AG\n\nVaccargiu, S\n\nvan Dam, RM\n\nvan der Harst, P\n\nvan Duijn, CM\n\nVelez Edward, DR\n\nVerweij, N\n\nVogelezang, S\n\nV ...\n\nBeiträge in Fachzeitschriften\nISI:000469996900008\n31152163.0\n10.1038/s41588-019-0407-x\nPMC6698888\nChronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1, 46, 70), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416, 78). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452, 64 independent individuals. Colocalization analyses of associations with eGFR among 783, 78 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.\n\nHofer, Edith\n\nMärz, Winfried\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n102429\nMeaningful interpretation of subdiffusive measurements in living cells (crowded environment) by fluorescence fluctuation microscopy.\n\nBaumann, G\n\nPlace, RF\n\nFöldes-Papp, Z\n\nBeiträge in Fachzeitschriften\nISI:000280473800014\n20553227.0\n10.2174/138920110791591454\nPMC3583073\nIn living cell or its nucleus, the motions of molecules are complicated due to the large crowding and expected heterogeneity of the intracellular environment. Randomness in cellular systems can be either spatial (anomalous) or temporal (heterogeneous). In order to separate both processes, we introduce anomalous random walks on fractals that represented crowded environments. We report the use of numerical simulation and experimental data of single-molecule detection by fluorescence fluctuation microscopy for detecting resolution limits of different mobile fractions in crowded environment of living cells. We simulate the time scale behavior of diffusion times tau(D)(tau) for one component, e.g. the fast mobile fraction, and a second component, e.g. the slow mobile fraction. The less the anomalous exponent alpha the higher the geometric crowding of the underlying structure of motion that is quantified by the ratio of the Hausdorff dimension and the walk exponent d(f)/d(w) and specific for the type of crowding generator used. The simulated diffusion time decreases for smaller values of alpha # 1 but increases for a larger time scale tau at a given value of alpha # 1. The effect of translational anomalous motion is substantially greater if alpha differs much from 1. An alpha value close to 1 contributes little to the time dependence of subdiffusive motions. Thus, quantitative determination of molecular weights from measured diffusion times and apparent diffusion coefficients, respectively, in temporal auto- and crosscorrelation analyses and from time-dependent fluorescence imaging data are difficult to interpret and biased in crowded environments of living cells and their cellular compartments; anomalous dynamics on different time scales tau must be coupled with the quantitative analysis of how experimental parameters change with predictions from simulated subdiffusive dynamics of molecular motions and mechanistic models. We first demonstrate that the crowding exponent alpha also determines the resolution of differences in diffusion times between two components in addition to photophysical parameters well-known for normal motion in dilute solution. The resolution limit between two different kinds of single molecule species is also analyzed under translational anomalous motion with broken ergodicity. We apply our theoretical predictions of diffusion times and lower limits for the time resolution of two components to fluorescence images in human prostate cancer cells transfected with GFP-Ago2 and GFP-Ago1. In order to mimic heterogeneous behavior in crowded environments of living cells, we need to introduce so-called continuous time random walks (CTRW). CTRWs were originally performed on regular lattice. This purely stochastic molecule behavior leads to subdiffusive motion with broken ergodicity in our simulations. For the first time, we are able to quantitatively differentiate between anomalous motion without broken ergodicity and anomalous motion with broken ergodicity in time-dependent fluorescence microscopy data sets of living cells. Since the experimental conditions to measure a selfsame molecule over an extended period of time, at which biology is taken place, in living cells or even in dilute solution are very restrictive, we need to perform the time average over a subpopulation of different single molecules of the same kind. For time averages over subpopulations of single molecules, the temporal auto- and crosscorrelation functions are first found. Knowing the crowding parameter alpha for the cell type and cellular compartment type, respectively, the heterogeneous parameter gamma can be obtained from the measurements in the presence of the interacting reaction partner, e.g. ligand, with the same alpha value. The product alpha x gamma = gamma is not a simple fitting parameter in the temporal auto- and two-color crosscorrelation functions because it is related to the proper physical models of anomalous (spatial) and heterogeneous (temporal) randomness in cellular systems.We have already derived an analytical solution gamma for in the special case of gamma = 3/2. In the case of two-color crosscorrelation or/and two-color fluorescence imaging (co-localization experiments), the second component is also a two-color species gr, for example a different molecular complex with an additional ligand. Here, we first show that plausible biological mechanisms from FCS/ FCCS and fluorescence imaging in living cells are highly questionable without proper quantitative physical models of subdiffusive motion and temporal randomness. At best, such quantitative FCS/ FCCS and fluorescence imaging data are difficult to interpret under crowding and heterogeneous conditions. It is challenging to translate proper physical models of anomalous (spatial) and heterogeneous (temporal) randomness in living cells and their cellular compartments like the nucleus into biological models of the cell biological process under study testable by single-molecule approaches. Otherwise, quantitative FCS/FCCS and fluorescence imaging measurements in living cells are not well described and cannot be interpreted in a meaningful way.\n\n\n"
},
{
"text": "\n186588\nWhat Is the Implant Survivorship and Functional Outcome After Total Humeral Replacement in Patients with Primary Bone Tumors?\n\nSchneider, KN\n\nBröking, JN\n\nGosheger, G\n\nLübben, T\n\nHardes, J\n\nSchorn, D\n\nSmolle, MA\n\nTheil, C\n\nAndreou, D\n\nBeiträge in Fachzeitschriften\nNone\n33595237.0\n10.1097/CORR.0000000000001677\nNone\nTotal humeral replacement is an option to reconstruct massive bone defects after resection of locally advanced bone tumors of the humerus. However, implant survivorship, potential risk factors for implant revision surgery, and functional results of total humeral replacement are poorly elucidated because of the rarity of the procedure.\n We asked: (1) What is the revision-free implant and overall limb survivorship after total humerus replacement? (2) What factors are associated with implant revision surgery? (3) What is the functional outcome of the procedure as determined by the Musculoskeletal Tumor Society (MSTS) score and the American Shoulder and Elbow Surgeons (ASES) score?\n Between August 1999 and December 2018, 666 patients underwent megaprosthetic reconstruction after resection of a primary malignant or locally aggressive/rarely metastasizing tumor of the long bones at our department. In all, 23% (154) of these patients had a primary tumor located in the humerus. During the study, we performed total humeral replacement in all patients with a locally advanced sarcoma, in patients with pathological fractures, in patients with skip metastases, or in patients with previous intralesional contaminating surgery, who would have no sufficient bone stock for a stable implant fixation for a single joint megaprosthetic replacement of the proximal or distal humerus. We performed no biological reconstructions or reconstructions with allograft-prosthetic composites. As a result, 5% (33 of 666) of patients underwent total humerus replacement. Six percent (2 of 33) of patients were excluded because they received a custom-made, three-dimensionally (3-D) printed hemiprosthesis, leaving 5% (31) of the initial 666 patients for inclusion in our retrospective analysis. Of these, 6% (2 of 31) had surgery more than 5 years ago, but they had not been seen in the last 5 years. Median (interquartile range) age at the time of surgery was 15 years (14 to 25 years), and indications for total humeral replacement were primary malignant bone tumors (n = 30) and a recurring, rarely metastasizing bone tumor (n = 1). All megaprosthetic reconstructions were performed with a single modular system. The implanted prostheses were silver-coated beginning in 2006, and beginning in 2010, a reverse proximal humerus component was used when appropriate. We analyzed endoprosthetic complications descriptively and assessed the functional outcome of all surviving patients who did not undergo secondary amputation using the 1993 MSTS score and the ASES score. The median (IQR) follow-up in all survivors was 75 months (50 to 122 months), with a minimum follow-up period of 25 months. We evaluated the following factors for possible association with implant revision surgery: age, BMI, reconstruction length, duration of surgery, extraarticular resection, pathological fracture, previous intralesional surgery, (neo-)adjuvant radio- and chemotherapy, and metastatic disease.\n The revision-free implant survivorship at 1 year was 77% (95% confidence interval 58% to 89%) and 74% (95% CI 55% to 86%) at 5 years. The overall limb survivorship was 93% (95% CI 75% to 98%) after 1 and after 5 years. We found revision-free survivorship to be lower in patients with extraarticular shoulder resection compared with intraarticular resections (50% [95% CI 21% to 74%] versus 89% [95% CI 64% to 97%]) after 5 years (subhazard ratios for extraarticular resections 4.4 [95% CI 1.2 to 16.5]; p = 0.03). With the number of patients available for our analysis, we could not detect a difference in revision-free survivorship at 5 years between patients who underwent postoperative radiotherapy (40% [95% CI 5% to 75%]) and patients who did not (81% [95% CI 60% to 92%]; p = 0.09). The median (IQR) MSTS score in 9 of 13 surviving patients after a median follow-up of 75 months (51 to 148 months) was 87% (67% to 92%), and the median ASES score was 83 (63 to 89) of 100 points, with higher scores representing better function.\n Total humeral replacement after resection of locally advanced bone tumors appears to be associated with a good functional outcome in patients who do not die of their tumors, which in our study was approximately one- third of those who were treated with a resection and total humerus prosthesis. However, the probability of early prosthetic revision surgery is high, especially in patients undergoing extraarticular resections, who should be counseled accordingly. Still, our results suggest that if the prosthesis survives the first year, further risk for revision appears to be low. Future studies should reexamine the effect of postoperative radiotherapy on implant survival in a larger cohort and evaluate whether the use of soft tissue coverage with plastic reconstructive surgery might decrease the risk of early revisions, especially in patients undergoing extraarticular resections.\n Level III, therapeutic study.\n Copyright © 2021 by the Association of Bone and Joint Surgeons.\n\nSmolle, Maria Anna\n\n\n"
},
{
"text": "\n175263\nCerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack: a pooled analysis of individual patient data from cohort studies.\n\nWilson, D\n\nAmbler, G\n\nLee, KJ\n\nLim, JS\n\nShiozawa, M\n\nKoga, M\n\nLi, L\n\nLovelock, C\n\nChabriat, H\n\nHennerici, M\n\nWong, YK\n\nMak, HKF\n\nPrats-Sánchez, L\n\nMartínez-Domeño, A\n\nInamura, S\n\nYoshifuji, K\n\nArsava, EM\n\nHorstmann, S\n\nPurrucker, J\n\nLam, BYK\n\nWong, A\n\nKim, YD\n\nSong, TJ\n\nSchrooten, M\n\nLemmens, R\n\nEppinger, S\n\nGattringer, T\n\nUysal, E\n\nTanriverdi, Z\n\nBornstein, NM\n\nAssayag, EB\n\nHallevi, H\n\nTanaka, J\n\nHara, H\n\nCoutts, SB\n\nHert, L\n\nPolymeris, A\n\nSeiffge, DJ\n\nLyrer, P\n\nAlgra, A\n\nKappelle, J\n\nAl-Shahi Salman, R\n\nJäger, HR\n\nLip, GYH\n\nMattle, HP\n\nPanos, LD\n\nMas, JL\n\nLegrand, L\n\nKarayiannis, C\n\nPhan, T\n\nGunkel, S\n\nChrist, N\n\nAbrigo, J\n\nLeung, T\n\nChu, W\n\nChappell, F\n\nMakin, S\n\nHayden, D\n\nWilliams, DJ\n\nKooi, ME\n\nvan Dam-Nolen, DHK\n\nBarbato, C\n\nBrowning, S\n\nWiegertjes, K\n\nTuladhar, AM\n\nMaaijwee, N\n\nGuevarra, C\n\nYatawara, C\n\nMendyk, AM\n\nDelmaire, C\n\nKöhler, S\n\nvan Oostenbrugge, R\n\nZhou, Y\n\nXu, C\n\nHilal, S\n\nGyanwali, B\n\nChen, C\n\nLou, M\n\nStaals, J\n\nBordet, R\n\nKandiah, N\n\nde Leeuw, FE\n\nSimister, R\n\nvan der Lugt, A\n\nKelly, PJ\n\nWardlaw, JM\n\nSoo, Y\n\nFluri, F\n\nSrikanth, V\n\nCalvet, D\n\nJung, S\n\nKwa, VIH\n\nEngelter, ST\n\nPeters, N\n\nSmith, EE\n\nYakushiji, Y\n\nOrken, DN\n\nFazekas, F\n\nThijs, V\n\nHeo, JH\n\nMok, V\n\nVeltkamp, R\n\nAy, H\n\nImaizumi, T\n\nGomez-Anson, B\n\nLau, KK\n\nJouvent, E\n\nRothwell, PM\n\nToyoda, K\n\nBae, HJ\n\nMarti-Fabregas, J\n\nWerring, DJ\n\nMicrobleeds International Collaborative Network\n\nBeiträge in Fachzeitschriften\nISI:000471176500014\n31130428.0\n10.1016/S1474-4422(19)30197-8\nPMC6562236\nCerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke.\n We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602.\n Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years).\n In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden.\n British Heart Foundation and UK Stroke Association.\n Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.\n\nEppinger, Sebastian\n\nFazekas, Franz\n\nGattringer, Thomas\n\n\n"
},
{
"text": "\n160566\nGenetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.\n\nAung, T\n\nOzaki, M\n\nLee, MC\n\nSchlötzer-Schrehardt, U\n\nThorleifsson, G\n\nMizoguchi, T\n\nIgo, RP\n\nHaripriya, A\n\nWilliams, SE\n\nAstakhov, YS\n\nOrr, AC\n\nBurdon, KP\n\nNakano, S\n\nMori, K\n\nAbu-Amero, K\n\nHauser, M\n\nLi, Z\n\nPrakadeeswari, G\n\nBailey, JNC\n\nCherecheanu, AP\n\nKang, JH\n\nNelson, S\n\nHayashi, K\n\nManabe, SI\n\nKazama, S\n\nZarnowski, T\n\nInoue, K\n\nIrkec, M\n\nCoca-Prados, M\n\nSugiyama, K\n\nJärvelä, I\n\nSchlottmann, P\n\nLerner, SF\n\nLamari, H\n\nNilgün, Y\n\nBikbov, M\n\nPark, KH\n\nCha, SC\n\nYamashiro, K\n\nZenteno, JC\n\nJonas, JB\n\nKumar, RS\n\nPerera, SA\n\nChan, ASY\n\nKobakhidze, N\n\nGeorge, R\n\nVijaya, L\n\nDo, T\n\nEdward, DP\n\nde Juan Marcos, L\n\nPakravan, M\n\nMoghimi, S\n\nIdeta, R\n\nBach-Holm, D\n\nKappelgaard, P\n\nWirostko, B\n\nThomas, S\n\nGaston, D\n\nBedard, K\n\nGreer, WL\n\nYang, Z\n\nChen, X\n\nHuang, L\n\nSang, J\n\nJia, H\n\nJia, L\n\nQiao, C\n\nZhang, H\n\nLiu, X\n\nZhao, B\n\nWang, YX\n\nXu, L\n\nLeruez, S\n\nReynier, P\n\nChichua, G\n\nTabagari, S\n\nUebe, S\n\nZenkel, M\n\nBerner, D\n\nMossböck, G\n\nWeisschuh, N\n\nHoja, U\n\nWelge-Luessen, UC\n\nMardin, C\n\nFounti, P\n\nChatzikyriakidou, A\n\nPappas, T\n\nAnastasopoulos, E\n\nLambropoulos, A\n\nGhosh, A\n\nShetty, R\n\nPorporato, N\n\nSaravanan, V\n\nVenkatesh, R\n\nShivkumar, C\n\nKalpana, N\n\nSarangapani, S\n\nKanavi, MR\n\nBeni, AN\n\nYazdani, S\n\nLashay, A\n\nNaderifar, H\n\nKhatibi, N\n\nFea, A\n\nLavia, C\n\nDallorto, L\n\nRolle, T\n\nFrezzotti, P\n\nPaoli, D\n\nSalvi, E\n\nManunta, P\n\nMori, Y\n\nMiyata, K\n\nHigashide, T\n\nChihara, E\n\nIshiko, S\n\nYoshida, A\n\nYanagi, M\n\nKiuchi, Y\n\nOhashi, T\n\nSakurai, T\n\nSugimoto, T\n\nChuman, H\n\nAihara, M\n\nInatani, M\n\nMiyake, M\n\nGotoh, N\n\nMatsuda, F\n\nYoshimura, N\n\nIkeda, Y\n\nUeno, M\n\nSotozono, C\n\nJeoung, JW\n\nSagong, M\n\nPark, KH\n\nAhn, J\n\nCruz-Aguilar, M\n\nEzzouhairi, SM\n\nRafei, A\n\nChong, YF\n\nNg, XY\n\nGoh, SR\n\nChen, Y\n\nYong, VHK\n\nKhan, MI\n\nOlawoye, OO\n\nAshaye, AO\n\nUgbede, I\n\nOnakoya, A\n\nKizor-Akaraiwe, N\n\nTeekhasaenee, C\n\nSuwan, Y\n\nSupakontanasan, W\n\nOkeke, S\n\nUche, NJ\n\nAsimadu, I\n\nAyub, H\n\nAkhtar, F\n\nKosior-Jarecka, E\n\nLukasik, U\n\nLischinsky, I\n\nCastro, V\n\nGrossmann, RP\n\nSunaric Megevand, G\n\nRoy, S\n\nDervan, E\n\nSilke, E\n\nRao, A\n\nSahay, P\n\nFornero, P\n\nCuello, O\n\nSivori, D\n\nZompa, T\n\nMills, RA\n\nSouzeau, E\n\nMitchell, P\n\nWang, JJ\n\nHewitt, AW\n\nCoote, M\n\nCrowston, JG\n\nAstakhov, SY\n\nAkopov, EL\n\nEmelyanov, A\n\nVysochinskaya, V\n\nKazakbaeva, G\n\nFayzrakhmanov, R\n\nAl-Obeidan, SA\n\nOwaidhah, O\n\nAljasim, LA\n\nChowbay, B\n\nFoo, JN\n\nSoh, RQ\n\nSim, KS\n\nXie, Z\n\nCheong, AWO\n\nMok, SQ\n\nSoo, HM\n\nChen, XY\n\nPeh, SQ\n\nHeng, KK\n\nHusain, R\n\nHo, SL\n\nHillmer, AM\n\nCheng, CY\n\nEscudero-Domínguez, FA\n\nGonzález-Sarmiento, R\n\nMartinon-Torres, F\n\nSalas, A\n\nPathanapitoon, K\n\nHansapinyo, L\n\nWanichwecharugruang, B\n\nKitnarong, N\n\nSakuntabhai, A\n\nNguyn, HX\n\nNguyn, GTT\n\nNguyn, TV\n\nZenz, W\n\nBinder, A\n\nKlobassa, DS\n\nHibberd, ML\n\nDavila, S\n\nHerms, S\n\nNöthen, MM\n\nMoebus, S\n\nRautenbach, RM\n\nZiskind, A\n\nCarmichael, TR\n\nRamsay, M\n\nÁlvarez, L\n\nGarcía, M\n\nGonzález-Iglesias, H\n\nRodríguez-Calvo, PP\n\nFernández-Vega Cueto, L\n\nOguz, Ç\n\nTamcelik, N\n\nAtalay, E\n\nBatu, B\n\nAktas, D\n\nKasım, B\n\nWilson, MR\n\nColeman, AL\n\nLiu, Y\n\nChalla, P\n\nHerndon, L\n\nKuchtey, RW\n\nKuchtey, J\n\nCurtin, K\n\nChaya, CJ\n\nCrandall, A\n\nZangwill, LM\n\nWong, TY\n\nNakano, M\n\nKinoshita, S\n\nden Hollander, AI\n\nVesti, E\n\nFingert, JH\n\nLee, RK\n\nSit, AJ\n\nShingleton, BJ\n\nWang, N\n\nCusi, D\n\nQamar, R\n\nKraft, P\n\nPericak-Vance, MA\n\nRaychaudhuri, S\n\nHeegaard, S\n\nKivelä, T\n\nReis, A\n\nKruse, FE\n\nWeinreb, RN\n\nPasquale, LR\n\nHaines, JL\n\nThorsteinsdottir, U\n\nJonasson, F\n\nAllingham, RR\n\nMilea, D\n\nRitch, R\n\nKubota, T\n\nTashiro, K\n\nVithana, EN\n\nMicheal, S\n\nTopouzis, F\n\nCraig, JE\n\nDubina, M\n\nSundaresan, P\n\nStefansson, K\n\nBeiträge in Fachzeitschriften\nISI:000404253300007\n28553957.0\n10.1038/ng.3875\nPMC6685441\nExfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.\n\nBinder, Alexander\n\nKohlfürst, Daniela\n\nZenz, Werner\n\n\n"
},
{
"text": "\n40101\nPlacebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. European Study Group on interferon beta-1b in secondary progressive MS.\n\nKappos, L\n\nPolman, C\n\nPozzilli, C\n\nThompson, A\n\nDahlke, F\n\nKnight R, Hern J, Coleman R, Gerrie L, Cooper G, Moore J, Boringa J, van Oosten B, Ronner H, Schrijver H, Truyen L, Montalban J, Rio J, Tintore M, Jacas C, Marzo E, Lechner-Scott J, Huber S, Lienert C, Brunnschweiler H, Hawkins S, Droogan A, McDonnell G, Duddy M, McKinstry S, Altenkirch H, Baum K, Einhaupl K, Marx P, Poewe W, Walter G, Akman H, Brockmeier B, Scherer P, Zschenderlein R, Schmierer K, Gelderblom H, Hartmann A, Stapf C, Luschow A, Mackert B, Schumacher H, Masuhr F, Hempel T, Zimmermann R, Munch M, Francis D, Heafield M, Al-Memar A, Winer J, Chong M, Brochet B, Gayou A, Auriacombe S, Dousset V, Wiles C, Thomas F, Pickersgill T, Hinds N, Dawson K, Hughes T, Hutchinson M, Murphy R, Redmond J, Webb S, Stoll G, Jander S, Hagemann G, Koller H, Hanemann C, Kolmel H, Reichel D, Petereit K, Thieme A, Khatami A, Neumann M, Amaducci L, Massacesi L, Siracusa G, Amato M, Bartolozzi L, Repice A, Minderhoud J, De Keyser J, Zorgdrager A, Zwanikken C, Poser S, Polak T, Gunther A, Bitsch A, Borner T, Weber F, Wikstrom J, Farkkila M, Majuri H, Sumelahti M, Telakivi T, Fredrikson S, Martin C, Miller D, O'Riordan J, Brex P, Kapoor R, Werring D, Confavreux C, Brunet P, Hannoun D, Brudon F, Moreau T, Blanc S, D'Hooghe M, Jacobs K, Lissoir F, Demonty L, Comi G, Colombo B, Rossi P, Rodegher M, Santuccio G, Martinelli F, Hohlfeld R, Walther E, Goebels N, Dang T, Lindert R, Voltz R, Cartlidge N, Bates D, Moran G, Pandit L, Westwood M, Haller P, Sommer J, Bitter J, Suss F, Mellies J, Mucha P, Lyon-Caen O, Degos JD, Roullet E, Lubetzki C, Creange A, Tourbah A, Pez D, Lecanuet P, Nicolt P, Edan G, Belliard S, De Marco O, Cahagne V, De Burghgraeve V, Brunet I, Fieschi C, Millefiorini E, Gasperini C, Buttinelli C, Frontini M, Howell S, Hadjivassiliou M, Gibson A, Graham A, Harkness K, Lawden M, Clanet M, Wauban E, Azais-Vuillemin C, Lau GKK, Louis C, Panelius M, Ruutiainen J, Eralinna J, Soilu-Hanninen M, Gold R, Hartung HP, Jung S, Bayas A, Flachenecker P, Weilbach F, Archelos J, Kollegger H, Vass K, Asenbaum S, Chatsakos T, Beckmann K, Ghazi M, Wagner K, Miltenburger C, McFarland H, Petkau J, Sabouraud O, Toyka K\n\nBeiträge in Fachzeitschriften\nISI:000076862300006\n9820296.0\n10.1016/S0140-6736(98)10039-9\nNone\nBACKGROUND: The beneficial effects of interferon beta have only been shown for patients in the relapsing-remitting phase of multiple sclerosis (MS). The role of interferon beta in the treatment of patients who are in the secondary progressive phase of the disease (SP-MS), and for whom no effective drug treatment is available, has not been assessed. METHODS: In this multicentre, double-masked, randomised, placebo-controlled trial, outpatients with SP-MS having scores of 3.0-6.5 on the Expanded Disability Status Scale (EDSS) received either 8 million IU interferon beta-1b every other day subcutaneously, or placebo, for up to 3 years. The primary outcome was the time to confirmed progression in disability as measured by a 1.0 point increase on the EDSS, sustained for at least 3 months, or a 0.5 point increase if the baseline EDSS was 6.0 or 6.5. A prospectively planned interim analysis of safety and efficacy of the intention-to-treat population was done after all patients had been in the study for at least 2 years. FINDINGS: 358 patients with SP-MS were allocated placebo and 360 were allocated interferon beta-1b; 57 patients (31 placebo, 26 interferon beta-1b) were lost to follow-up. There was a highly significant difference in time to confirmed progression of disability in favour of interferon beta-1b (p=0.0008). Interferon beta-1b delayed progression for 9-12 months in a study period of 2-3 years. The odds ratio for confirmed progression was 0.65 (95% CI 0.52-0.83). This beneficial effect was seen in patients with superimposed relapses and in patients who had only progressive deterioration without relapses. Positive results were also obtained regarding time to becoming wheelchair-bound, relapse rate and severity, number of steroid treatments and hospital admissions, as well as on magnetic resonance imaging variables. The drug was safe and side effects were in line with previous experience with interferon beta-1b. The study was stopped after the interim results gave clear evidence of efficacy. INTERPRETATION: Treatment with interferon beta-1b delays sustained neurological deterioration in patients with SP-MS. Interferon beta-1b is the first treatment to show a therapeutic effect in patients with SP-MS.\n\nArchelos-Garcia, Juan-Jose\n\n\n"
},
{
"text": "\n156557\nBuilding Bridges for Innovation in Ageing: Synergies between Action Groups of the EIP on AHA.\n\nBousquet, J\n\nBewick, M\n\nCano, A\n\nEklund, P\n\nFico, G\n\nGoswami, N\n\nGuldemond, NA\n\nHenderson, D\n\nHinkema, MJ\n\nLiotta, G\n\nMair, A\n\nMolloy, W\n\nMonaco, A\n\nMonsonis-Paya, I\n\nNizinska, A\n\nPapadopoulos, H\n\nPavlickova, A\n\nPecorelli, S\n\nPrados-Torres, A\n\nRoller-Wirnsberger, RE\n\nSomekh, D\n\nVera-Muñoz, C\n\nVisser, F\n\nFarrell, J\n\nMalva, J\n\nAndersen Ranberg, K\n\nCamuzat, T\n\nCarriazo, AM\n\nCrooks, G\n\nGutter, Z\n\nIaccarino, G\n\nManuel de Keenoy, E\n\nModa, G\n\nRodriguez-Mañas, L\n\nVontetsianos, T\n\nAbreu, C\n\nAlonso, J\n\nAlonso-Bouzon, C\n\nAnkri, J\n\nArredondo, MT\n\nAvolio, F\n\nBedbrook, A\n\nBiałoszewski, AZ\n\nBlain, H\n\nBourret, R\n\nCabrera-Umpierrez, MF\n\nCatala, A\n\nO'Caoimh, R\n\nCesari, M\n\nChavannes, NH\n\nCorreia-da-Sousa, J\n\nDedeu, T\n\nFerrando, M\n\nFerri, M\n\nFokkens, WJ\n\nGarcia-Lizana, F\n\nGuérin, O\n\nHellings, PW\n\nHaahtela, T\n\nIllario, M\n\nInzerilli, MC\n\nLodrup Carlsen, KC\n\nKardas, P\n\nKeil, T\n\nMaggio, M\n\nMendez-Zorrilla, A\n\nMenditto, E\n\nMercier, J\n\nMichel, JP\n\nMurray, R\n\nNogues, M\n\nO'Byrne-Maguire, I\n\nPappa, D\n\nParent, AS\n\nPastorino, M\n\nRobalo-Cordeiro, C\n\nSamolinski, B\n\nSiciliano, P\n\nTeixeira, AM\n\nTsartara, SI\n\nValiulis, A\n\nVandenplas, O\n\nVasankari, T\n\nVellas, B\n\nVollenbroek-Hutten, M\n\nWickman, M\n\nYorgancioglu, A\n\nZuberbier, T\n\nBarbagallo, M\n\nCanonica, GW\n\nKlimek, L\n\nMaggi, S\n\nAberer, W\n\nAkdis, C\n\nAdcock, IM\n\nAgache, I\n\nAlbera, C\n\nAlonso-Trujillo, F\n\nAngel Guarcia, M\n\nAnnesi-Maesano, I\n\nApostolo, J\n\nArshad, SH\n\nAttalin, V\n\nAvignon, A\n\nBachert, C\n\nBaroni, I\n\nBel, E\n\nBenson, M\n\nBescos, C\n\nBlasi, F\n\nBarbara, C\n\nBergmann, KC\n\nBernard, PL\n\nBonini, S\n\nBousquet, PJ\n\nBranchini, B\n\nBrightling, CE\n\nBruguière, V\n\nBunu, C\n\nBush, A\n\nCaimmi, DP\n\nCalderon, MA\n\nCanovas, G\n\nCardona, V\n\nCarlsen, KH\n\nCesario, A\n\nChkhartishvili, E\n\nChiron, R\n\nChivato, T\n\nChung, KF\n\nd'Angelantonio, M\n\nDe Carlo, G\n\nCholley, D\n\nChorin, F\n\nCombe, B\n\nCompas, B\n\nCosta, DJ\n\nCosta, E\n\nCoste, O\n\nCoupet, AL\n\nCrepaldi, G\n\nCustovic, A\n\nDahl, R\n\nDahlen, SE\n\nDemoly, P\n\nDevillier, P\n\nDidier, A\n\nDinh-Xuan, AT\n\nDjukanovic, R\n\nDokic, D\n\nDu Toit, G\n\nDubakiene, R\n\nDupeyron, A\n\nEmuzyte, R\n\nFiocchi, A\n\nWagner, A\n\nFletcher, M\n\nFonseca, J\n\nFougère, B\n\nGamkrelidze, A\n\nGarces, G\n\nGarcia-Aymeric, J\n\nGarcia-Zapirain, B\n\nGemicioğlu, B\n\nGouder, C\n\nHellquist-Dahl, B\n\nHermosilla-Gimeno, I\n\nHéve, D\n\nHolland, C\n\nHumbert, M\n\nHyland, M\n\nJohnston, SL\n\nJust, J\n\nJutel, M\n\nKaidashev, IP\n\nKhaitov, M\n\nKalayci, O\n\nKalyoncu, AF\n\nKeijser, W\n\nKerstjens, H\n\nKnezović, J\n\nKowalski, M\n\nKoppelman, GH\n\nKotska, T\n\nKovac, M\n\nKull, I\n\nKuna, P\n\nKvedariene, V\n\nLepore, V\n\nMacNee, W\n\nMaggio, M\n\nMagnan, A\n\nMajer, I\n\nManning, P\n\nMarcucci, M\n\nMarti, T\n\nMasoli, M\n\nMelen, E\n\nMiculinic, N\n\nMihaltan, F\n\nMilenkovic, B\n\nMillot-Keurinck, J\n\nMlinarić, H\n\nMomas, I\n\nMontefort, S\n\nMorais-Almeida, M\n\nMoreno-Casbas, T\n\nMösges, R\n\nMullol, J\n\nNadif, R\n\nNalin, M\n\nNavarro-Pardo, E\n\nNekam, K\n\nNinot, G\n\nPaccard, D\n\nPais, S\n\nPalummeri, E\n\nPanzner, P\n\nPapadopoulos, NK\n\nPapanikolaou, C\n\nPassalacqua, G\n\nPastor, E\n\nPerrot, M\n\nPlavec, D\n\nPopov, TA\n\nPostma, DS\n\nPrice, D\n\nRaffort, N\n\nReuzeau, JC\n\nRobine, JM\n\nRodenas, F\n\nRobusto, F\n\nRoche, N\n\nRomano, A\n\nRomano, V\n\nRosado-Pinto, J\n\nRoubille, F\n\nRuiz, F\n\nRyan, D\n\nSalcedo, T\n\nSchmid-Grendelmeier, P\n\nSchulz, H\n\nSchunemann, HJ\n\nSerrano, E\n\nSheikh, A\n\nShields, M\n\nSiafakas, N\n\nScichilone, N\n\nSiciliano, P\n\nSkrindo, I\n\nSmit, HA\n\nSourdet, S\n\nSousa-Costa, E\n\nSpranger, O\n\nSooronbaev, T\n\nSruk, V\n\nSterk, PJ\n\nTodo-Bom, A\n\nTouchon, J\n\nTramontano, D\n\nTriggiani, M\n\nTsartara, SI\n\nValero, AL\n\nValovirta, E\n\nvan Ganse, E\n\nvan Hage, M\n\nvan den Berge, M\n\nVandenplas, O\n\nVe ...\n\nBeiträge in Fachzeitschriften\nISI:000394347000013\n27999855.0\n10.1007/s12603-016-0803-1\nNone\nThe Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).\n\nAberer, Werner\n\nGoswami, Nandu\n\nRoller-Wirnsberger, Regina\n\n\n"
},
{
"text": "\n173835\nGenetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.\n\nKunkle, BW\n\nGrenier-Boley, B\n\nSims, R\n\nBis, JC\n\nDamotte, V\n\nNaj, AC\n\nBoland, A\n\nVronskaya, M\n\nvan der Lee, SJ\n\nAmlie-Wolf, A\n\nBellenguez, C\n\nFrizatti, A\n\nChouraki, V\n\nMartin, ER\n\nSleegers, K\n\nBadarinarayan, N\n\nJakobsdottir, J\n\nHamilton-Nelson, KL\n\nMoreno-Grau, S\n\nOlaso, R\n\nRaybould, R\n\nChen, Y\n\nKuzma, AB\n\nHiltunen, M\n\nMorgan, T\n\nAhmad, S\n\nVardarajan, BN\n\nEpelbaum, J\n\nHoffmann, P\n\nBoada, M\n\nBeecham, GW\n\nGarnier, JG\n\nHarold, D\n\nFitzpatrick, AL\n\nValladares, O\n\nMoutet, ML\n\nGerrish, A\n\nSmith, AV\n\nQu, L\n\nBacq, D\n\nDenning, N\n\nJian, X\n\nZhao, Y\n\nDel Zompo, M\n\nFox, NC\n\nChoi, SH\n\nMateo, I\n\nHughes, JT\n\nAdams, HH\n\nMalamon, J\n\nSanchez-Garcia, F\n\nPatel, Y\n\nBrody, JA\n\nDombroski, BA\n\nNaranjo, MCD\n\nDaniilidou, M\n\nEiriksdottir, G\n\nMukherjee, S\n\nWallon, D\n\nUphill, J\n\nAspelund, T\n\nCantwell, LB\n\nGarzia, F\n\nGalimberti, D\n\nHofer, E\n\nButkiewicz, M\n\nFin, B\n\nScarpini, E\n\nSarnowski, C\n\nBush, WS\n\nMeslage, S\n\nKornhuber, J\n\nWhite, CC\n\nSong, Y\n\nBarber, RC\n\nEngelborghs, S\n\nSordon, S\n\nVoijnovic, D\n\nAdams, PM\n\nVandenberghe, R\n\nMayhaus, M\n\nCupples, LA\n\nAlbert, MS\n\nDe Deyn, PP\n\nGu, W\n\nHimali, JJ\n\nBeekly, D\n\nSquassina, A\n\nHartmann, AM\n\nOrellana, A\n\nBlacker, D\n\nRodriguez-Rodriguez, E\n\nLovestone, S\n\nGarcia, ME\n\nDoody, RS\n\nMunoz-Fernadez, C\n\nSussams, R\n\nLin, H\n\nFairchild, TJ\n\nBenito, YA\n\nHolmes, C\n\nKaramujić-Čomić, H\n\nFrosch, MP\n\nThonberg, H\n\nMaier, W\n\nRoschupkin, G\n\nGhetti, B\n\nGiedraitis, V\n\nKawalia, A\n\nLi, S\n\nHuebinger, RM\n\nKilander, L\n\nMoebus, S\n\nHernández, I\n\nKamboh, MI\n\nBrundin, R\n\nTurton, J\n\nYang, Q\n\nKatz, MJ\n\nConcari, L\n\nLord, J\n\nBeiser, AS\n\nKeene, CD\n\nHelisalmi, S\n\nKloszewska, I\n\nKukull, WA\n\nKoivisto, AM\n\nLynch, A\n\nTarraga, L\n\nLarson, EB\n\nHaapasalo, A\n\nLawlor, B\n\nMosley, TH\n\nLipton, RB\n\nSolfrizzi, V\n\nGill, M\n\nLongstreth, WT\n\nMontine, TJ\n\nFrisardi, V\n\nDiez-Fairen, M\n\nRivadeneira, F\n\nPetersen, RC\n\nDeramecourt, V\n\nAlvarez, I\n\nSalani, F\n\nCiaramella, A\n\nBoerwinkle, E\n\nReiman, EM\n\nFievet, N\n\nRotter, JI\n\nReisch, JS\n\nHanon, O\n\nCupidi, C\n\nAndre Uitterlinden, AG\n\nRoyall, DR\n\nDufouil, C\n\nMaletta, RG\n\nde Rojas, I\n\nSano, M\n\nBrice, A\n\nCecchetti, R\n\nGeorge-Hyslop, PS\n\nRitchie, K\n\nTsolaki, M\n\nTsuang, DW\n\nDubois, B\n\nCraig, D\n\nWu, CK\n\nSoininen, H\n\nAvramidou, D\n\nAlbin, RL\n\nFratiglioni, L\n\nGermanou, A\n\nApostolova, LG\n\nKeller, L\n\nKoutroumani, M\n\nArnold, SE\n\nPanza, F\n\nGkatzima, O\n\nAsthana, S\n\nHannequin, D\n\nWhitehead, P\n\nAtwood, CS\n\nCaffarra, P\n\nHampel, H\n\nQuintela, I\n\nCarracedo, Á\n\nLannfelt, L\n\nRubinsztein, DC\n\nBarnes, LL\n\nPasquier, F\n\nFrölich, L\n\nBarral, S\n\nMcGuinness, B\n\nBeach, TG\n\nJohnston, JA\n\nBecker, JT\n\nPassmore, P\n\nBigio, EH\n\nSchott, JM\n\nBird, TD\n\nWarren, JD\n\nBoeve, BF\n\nLupton, MK\n\nBowen, JD\n\nProitsi, P\n\nBoxer, A\n\nPowell, JF\n\nBurke, JR\n\nKauwe, JSK\n\nBurns, JM\n\nMancuso, M\n\nBuxbaum, JD\n\nBonuccelli, U\n\nCairns, NJ\n\nMcQuillin, A\n\nCao, C\n\nLivingston, G\n\nCarlson, CS\n\nBass, NJ\n\nCarlsson, CM\n\nHardy, J\n\nCarney, RM\n\nBras, J\n\nCarrasquillo, MM\n\nGuerreiro, R\n\nAllen, M\n\nChui, HC\n\nFisher, E\n\nMasullo, C\n\nCrocco, EA\n\nDeCarli, C\n\nBisceglio, G\n\nDick, M\n\nMa, L\n\nDuara, R\n\nGraff-Radford, NR\n\nEvans, DA\n\nHodges, A\n\nFaber, KM\n\nScherer, M\n\nFallon, KB\n\nRiemenschneider, M\n\nFardo, DW\n\nHeun, R\n\nFarlow, MR\n\nKölsch, H\n\nFerris, S\n\nLeber, M\n\nForoud, TM\n\nHeuser, I\n\nGalasko, DR\n\nGiegling, I\n\nGearing, M\n\nHüll, M\n\nGeschwind, DH\n\nGilbert, JR\n\nMorris, J\n\nGreen, RC\n\nMayo, K\n\nGrowdon, JH\n\nFeulner, T\n\nHamilton, RL\n\nHarrell, LE\n\nDrichel, D\n\nHonig, LS\n\nCushion, TD\n\nHuentelman, MJ\n\nHollingworth, P\n\nHulette, CM\n\nHyman, BT\n\nMarshall, R\n\nJarvik, GP\n\nMeggy, A\n\nAbner, E\n\nMenzies, GE\n\nJin, LW\n\nLeonenko, G\n\nReal, LM\n\nJun, GR\n\nBaldwin, CT ...\n\nBeiträge in Fachzeitschriften\nISI:000459947200011\n30820047.0\n10.1038/s41588-019-0358-2\nPMC6463297\nRisk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94, 37 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education.\n\nHofer, Edith\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n114080\nGenetic variants in novel pathways influence blood pressure and cardiovascular disease risk.\n\nInternational Consortium for Blood Pressure Genome-Wide Association Studies\n\nEhret, GB\n\nMunroe, PB\n\nRice, KM\n\nBochud, M\n\nJohnson, AD\n\nChasman, DI\n\nSmith, AV\n\nTobin, MD\n\nVerwoert, GC\n\nHwang, SJ\n\nPihur, V\n\nVollenweider, P\n\nO'Reilly, PF\n\nAmin, N\n\nBragg-Gresham, JL\n\nTeumer, A\n\nGlazer, NL\n\nLauner, L\n\nZhao, JH\n\nAulchenko, Y\n\nHeath, S\n\nSõber, S\n\nParsa, A\n\nLuan, J\n\nArora, P\n\nDehghan, A\n\nZhang, F\n\nLucas, G\n\nHicks, AA\n\nJackson, AU\n\nPeden, JF\n\nTanaka, T\n\nWild, SH\n\nRudan, I\n\nIgl, W\n\nMilaneschi, Y\n\nParker, AN\n\nFava, C\n\nChambers, JC\n\nFox, ER\n\nKumari, M\n\nGo, MJ\n\nvan der Harst, P\n\nKao, WH\n\nSjögren, M\n\nVinay, DG\n\nAlexander, M\n\nTabara, Y\n\nShaw-Hawkins, S\n\nWhincup, PH\n\nLiu, Y\n\nShi, G\n\nKuusisto, J\n\nTayo, B\n\nSeielstad, M\n\nSim, X\n\nNguyen, KD\n\nLehtimäki, T\n\nMatullo, G\n\nWu, Y\n\nGaunt, TR\n\nOnland-Moret, NC\n\nCooper, MN\n\nPlatou, CG\n\nOrg, E\n\nHardy, R\n\nDahgam, S\n\nPalmen, J\n\nVitart, V\n\nBraund, PS\n\nKuznetsova, T\n\nUiterwaal, CS\n\nAdeyemo, A\n\nPalmas, W\n\nCampbell, H\n\nLudwig, B\n\nTomaszewski, M\n\nTzoulaki, I\n\nPalmer, ND\n\nCARDIoGRAM consortium\n\nCKDGen Consortium\n\nKidneyGen Consortium\n\nEchoGen consortium\n\nCHARGE-HF consortium\n\nAspelund, T\n\nGarcia, M\n\nChang, YP\n\nO'Connell, JR\n\nSteinle, NI\n\nGrobbee, DE\n\nArking, DE\n\nKardia, SL\n\nMorrison, AC\n\nHernandez, D\n\nNajjar, S\n\nMcArdle, WL\n\nHadley, D\n\nBrown, MJ\n\nConnell, JM\n\nHingorani, AD\n\nDay, IN\n\nLawlor, DA\n\nBeilby, JP\n\nLawrence, RW\n\nClarke, R\n\nHopewell, JC\n\nOngen, H\n\nDreisbach, AW\n\nLi, Y\n\nYoung, JH\n\nBis, JC\n\nKähönen, M\n\nViikari, J\n\nAdair, LS\n\nLee, NR\n\nChen, MH\n\nOlden, M\n\nPattaro, C\n\nBolton, JA\n\nKöttgen, A\n\nBergmann, S\n\nMooser, V\n\nChaturvedi, N\n\nFrayling, TM\n\nIslam, M\n\nJafar, TH\n\nErdmann, J\n\nKulkarni, SR\n\nBornstein, SR\n\nGrässler, J\n\nGroop, L\n\nVoight, BF\n\nKettunen, J\n\nHoward, P\n\nTaylor, A\n\nGuarrera, S\n\nRicceri, F\n\nEmilsson, V\n\nPlump, A\n\nBarroso, I\n\nKhaw, KT\n\nWeder, AB\n\nHunt, SC\n\nSun, YV\n\nBergman, RN\n\nCollins, FS\n\nBonnycastle, LL\n\nScott, LJ\n\nStringham, HM\n\nPeltonen, L\n\nPerola, M\n\nVartiainen, E\n\nBrand, SM\n\nStaessen, JA\n\nWang, TJ\n\nBurton, PR\n\nSoler Artigas, M\n\nDong, Y\n\nSnieder, H\n\nWang, X\n\nZhu, H\n\nLohman, KK\n\nRudock, ME\n\nHeckbert, SR\n\nSmith, NL\n\nWiggins, KL\n\nDoumatey, A\n\nShriner, D\n\nVeldre, G\n\nViigimaa, M\n\nKinra, S\n\nPrabhakaran, D\n\nTripathy, V\n\nLangefeld, CD\n\nRosengren, A\n\nThelle, DS\n\nCorsi, AM\n\nSingleton, A\n\nForrester, T\n\nHilton, G\n\nMcKenzie, CA\n\nSalako, T\n\nIwai, N\n\nKita, Y\n\nOgihara, T\n\nOhkubo, T\n\nOkamura, T\n\nUeshima, H\n\nUmemura, S\n\nEyheramendy, S\n\nMeitinger, T\n\nWichmann, HE\n\nCho, YS\n\nKim, HL\n\nLee, JY\n\nScott, J\n\nSehmi, JS\n\nZhang, W\n\nHedblad, B\n\nNilsson, P\n\nSmith, GD\n\nWong, A\n\nNarisu, N\n\nStančáková, A\n\nRaffel, LJ\n\nYao, J\n\nKathiresan, S\n\nO'Donnell, CJ\n\nSchwartz, SM\n\nIkram, MA\n\nLongstreth, WT\n\nMosley, TH\n\nSeshadri, S\n\nShrine, NR\n\nWain, LV\n\nMorken, MA\n\nSwift, AJ\n\nLaitinen, J\n\nProkopenko, I\n\nZitting, P\n\nCooper, JA\n\nHumphries, SE\n\nDanesh, J\n\nRasheed, A\n\nGoel, A\n\nHamsten, A\n\nWatkins, H\n\nBakker, SJ\n\nvan Gilst, WH\n\nJanipalli, CS\n\nMani, KR\n\nYajnik, CS\n\nHofman, A\n\nMattace-Raso, FU\n\nOostra, BA\n\nDemirkan, A\n\nIsaacs, A\n\nRivadeneira, F\n\nLakatta, EG\n\nOrru, M\n\nScuteri, A\n\nAla-Korpela, M\n\nKangas, AJ\n\nLyytikäinen, LP\n\nSoininen, P\n\nTukiainen, T\n\nWürtz, P\n\nOng, RT\n\nDörr, M\n\nKroemer, HK\n\nVölker, U\n\nVölzke, H\n\nGalan, P\n\nHercberg, S\n\nLathrop, M\n\nZelenika, D\n\nDeloukas, P\n\nMangino, M\n\nSpector, TD\n\nZhai, G\n\nMeschia, JF\n\nNalls, MA\n\nSharma, P\n\nTerzic, J\n\nKumar, MV\n\nDenniff, M\n\nZukowska-Szczechowska, E\n\nWagenknecht, LE\n\nFowkes, FG\n\nCharchar, FJ\n\nSchwarz, PE\n\nHayward, C\n\nGuo, X\n\nRotimi, C\n\nBots, ML\n\nBrand, E\n\nSamani, NJ\n\nPolasek, O\n\nTalmud, PJ\n\nNyberg, F\n\nKuh, D\n\nLaan, M\n\n...\n\nBeiträge in Fachzeitschriften\nISI:000295575400043\n21909115.0\n10.1038/nature10405\nPMC3340926\nBlood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200, 00 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.\n\nCavalieri, Margherita\n\nMärz, Winfried\n\nMeinitzer, Andreas\n\nPilz, Stefan\n\nRenner, Wilfried\n\nScharnagl, Hubert\n\nSchmidt, Helena\n\nSchmidt, Reinhold\n\n\n"
},
{
"text": "\n187860\nGenome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology\n\nMullins, N\n\nForstner, AJ\n\nO'Connell, KS\n\nCoombes, B\n\nColeman, JRI\n\nQiao, Z\n\nAls, TD\n\nBigdeli, TB\n\nBorte, S\n\nBryois, J\n\nCharney, AW\n\nDrange, OK\n\nGandal, MJ\n\nHagenaars, SP\n\nIkeda, M\n\nKamitaki, N\n\nKim, M\n\nKrebs, K\n\nPanagiotaropoulou, G\n\nSchilder, BM\n\nSloofman, LG\n\nSteinberg, S\n\nTrubetskoy, V\n\nWinsvold, BS\n\nWon, HH\n\nAbramova, L\n\nAdorjan, K\n\nAgerbo, E\n\nAl Eissa, M\n\nAlbani, D\n\nAlliey-Rodriguez, N\n\nAnjorin, A\n\nAntilla, V\n\nAntoniou, A\n\nAwasthi, S\n\nBaek, JH\n\nBaekvad-Hansen, M\n\nBass, N\n\nBauer, M\n\nBeins, EC\n\nBergen, SE\n\nBirner, A\n\nPedersen, CB\n\nBoen, E\n\nBoks, MP\n\nBosch, R\n\nBrum, M\n\nBrumpton, B\n\nBrunkhorst-Kanaan, N\n\nBudde, M\n\nBybjerg-Grauholm, J\n\nByerley, W\n\nCairns, M\n\nCasas, M\n\nCervantes, P\n\nClarke, TK\n\nCruceanu, C\n\nCuellar-Barboza, A\n\nCunningham, J\n\nCurtis, D\n\nCzerski, PM\n\nDale, AM\n\nDalkner, N\n\nDavid, FS\n\nDegenhardt, F\n\nDjurovic, S\n\nDobbyn, AL\n\nDouzenis, A\n\nElvsashagen, T\n\nEscott-Price, V\n\nFerrier, IN\n\nFiorentino, A\n\nForoud, TM\n\nForty, L\n\nFrank, J\n\nFrei, O\n\nFreimer, NB\n\nFrisen, L\n\nGade, K\n\nGarnham, J\n\nGelernter, J\n\nPedersen, MG\n\nGizer, IR\n\nGordon, SD\n\nGordon-Smith, K\n\nGreenwood, TA\n\nGrove, J\n\nGuzman-Parra, J\n\nHa, K\n\nHaraldsson, M\n\nHautzinger, M\n\nHeilbronner, U\n\nHellgren, D\n\nHerms, S\n\nHoffmann, P\n\nHolmans, PA\n\nHuckins, L\n\nJamain, S\n\nJohnson, JS\n\nKalman, JL\n\nKamatani, Y\n\nKennedy, JL\n\nKittel-Schneider, S\n\nKnowles, JA\n\nKogevinas, M\n\nKoromina, M\n\nKranz, TM\n\nKranzler, HR\n\nKubo, M\n\nKupka, R\n\nKushner, SA\n\nLavebratt, C\n\nLawrence, J\n\nLeber, M\n\nLee, HJ\n\nLee, PH\n\nLevy, SE\n\nLewis, C\n\nLiao, C\n\nLucae, S\n\nLundberg, M\n\nMacIntyre, DJ\n\nMaier, W\n\nMaihofer, A\n\nMalaspina, D\n\nMaratou, E\n\nMartinsson, L\n\nMattheisen, M\n\nMcCarroll, SA\n\nMcGregor, NW\n\nMcGuffin, P\n\nMcKay, JD\n\nMedeiros, H\n\nMedland, SE\n\nMillischer, V\n\nMontgomery, GW\n\nMoran, JL\n\nMorris, DW\n\nMuhleisen, TW\n\nO'Brien, N\n\nO'Donovan, C\n\nLoohuis, LMO\n\nOruc, L\n\nPapiol, S\n\nPardinas, AF\n\nPerry, A\n\nPfennig, A\n\nPorichi, E\n\nPotash, JB\n\nQuested, D\n\nRaj, T\n\nRapaport, MH\n\nDePaulo, JR\n\nRegeer, EJ\n\nRice, JP\n\nRivas, F\n\nRivera, M\n\nRoth, J\n\nRoussos, P\n\nRuderfer, DM\n\nSanchez-Mora, C\n\nSchulte, EC\n\nSenner, F\n\nSharp, S\n\nShilling, PD\n\nSigurdsson, E\n\nSirignano, L\n\nSlaney, C\n\nSmeland, OB\n\nSobell, JL\n\nHansen, CS\n\nArtigas, MS\n\nSpijker, AT\n\nStein, DJ\n\nStrauss, JS\n\nSwiatkowska, B\n\nTerao, C\n\nThorgeirsson, TE\n\nToma, C\n\nTooney, P\n\nTsermpini, EE\n\nVawter, MP\n\nVedder, H\n\nWalters, JTR\n\nWitt, SH\n\nXi, S\n\nXu, W\n\nYang, JMK\n\nYoung, AH\n\nYoung, H\n\nZandi, PP\n\nZhou, H\n\nZillich, L\n\nAdolfsson, R\n\nAgartz, I\n\nAlda, M\n\nAlfredsson, L\n\nBabadjanova, G\n\nBacklund, L\n\nBaune, BT\n\nBellivier, F\n\nBengesser, S\n\nBerrettini, WH\n\nBlackwood, DHR\n\nBoehnke, M\n\nBorglum, AD\n\nBreen, G\n\nCarr, VJ\n\nCatts, S\n\nCorvin, A\n\nCraddock, N\n\nDannlowski, U\n\nDikeos, D\n\nEsko, T\n\nEtain, B\n\nFerentinos, P\n\nFrye, M\n\nFullerton, JM\n\nGawlik, M\n\nGershon, ES\n\nGoes, F\n\nGreen, MJ\n\nGrigoroiu-Serbanescu, M\n\nHauser, J\n\nHenskens, F\n\nHillert, J\n\nHong, KS\n\nHougaard, DM\n\nHultman, CM\n\nHveem, K\n\nIwata, N\n\nJablensky, AV\n\nJones, I\n\nJones, LA\n\nKahn, RS\n\nKelsoe, JR\n\nKirov, G\n\nLanden, M\n\nLeboyer, M\n\nLewis, CM\n\nLi, QS\n\nLissowska, J\n\nLochner, C\n\nLoughland, C\n\nMartin, NG\n\nMathews, CA\n\nMayoral, F\n\nMcElroy, SL\n\nMcIntosh, AM\n\nMcMahon, FJ\n\nMelle, I\n\nMichie, P\n\nMilani, L\n\nMitchell, PB\n\nMorken, G\n\nMors, O\n\nMortensen, PB\n\nMowry, B\n\nMuller-Myhsok, B\n\nMyers, RM\n\nNeale, BM\n\nNievergelt, CM\n\nNordentoft, M\n\nNothen, MM\n\nODonovan, MC\n\nOedegaard, KJ\n\nOlsson, T\n\nOwen, MJ\n\nPaciga, SA\n\nPantelis, C\n\nPato, C\n\nPato, MT\n\nPatrinos, GP\n\nPerlis, RH\n\nPosthuma, D\n\nRamos-Quiroga, JA\n\nReif, A\n\nReininghaus, EZ\n\nRibases, M\n\nRietschel, M\n\nRipke, S\n\nRouleau,\n\nBeiträge in Fachzeitschriften\nISI:000651382200001\n34002096.0\n10.1038/s41588-021-00857-4\nNone\nBipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41, 17 bipolar disorder cases and 371, 49 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. Genome-wide association analyses of 41, 17 bipolar disorder cases and 371, 49 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.\n\nBengesser, Susanne\n\nBirner, Armin\n\nDalkner, Nina\n\nReininghaus, Eva\n\n\n"
},
{
"text": "\n176826\nNext-generation ARIA care pathways for rhinitis and asthma: a model for multimorbid chronic diseases.\n\nBousquet, JJ\n\nSchünemann, HJ\n\nTogias, A\n\nErhola, M\n\nHellings, PW\n\nZuberbier, T\n\nAgache, I\n\nAnsotegui, IJ\n\nAnto, JM\n\nBachert, C\n\nBecker, S\n\nBedolla-Barajas, M\n\nBewick, M\n\nBosnic-Anticevich, S\n\nBosse, I\n\nBoulet, LP\n\nBourrez, JM\n\nBrusselle, G\n\nChavannes, N\n\nCosta, E\n\nCruz, AA\n\nCzarlewski, W\n\nFokkens, WJ\n\nFonseca, JA\n\nGaga, M\n\nHaahtela, T\n\nIllario, M\n\nKlimek, L\n\nKuna, P\n\nKvedariene, V\n\nLe, LTT\n\nLarenas-Linnemann, D\n\nLaune, D\n\nLourenço, OM\n\nMenditto, E\n\nMullol, J\n\nOkamoto, Y\n\nPapadopoulos, N\n\nPham-Thi, N\n\nPicard, R\n\nPinnock, H\n\nRoche, N\n\nRoller-Wirnsberger, RE\n\nRolland, C\n\nSamolinski, B\n\nSheikh, A\n\nToppila-Salmi, S\n\nTsiligianni, I\n\nValiulis, A\n\nValovirta, E\n\nVasankari, T\n\nVentura, MT\n\nWalker, S\n\nWilliams, S\n\nAkdis, CA\n\nAnnesi-Maesano, I\n\nArnavielhe, S\n\nBasagana, X\n\nBateman, E\n\nBedbrook, A\n\nBennoor, KS\n\nBenveniste, S\n\nBergmann, KC\n\nBialek, S\n\nBillo, N\n\nBindslev-Jensen, C\n\nBjermer, L\n\nBlain, H\n\nBonini, M\n\nBonniaud, P\n\nBouchard, J\n\nBriedis, V\n\nBrightling, CE\n\nBrozek, J\n\nBuhl, R\n\nBuonaiuto, R\n\nCanonica, GW\n\nCardona, V\n\nCarriazo, AM\n\nCarr, W\n\nCartier, C\n\nCasale, T\n\nCecchi, L\n\nCepeda Sarabia, AM\n\nChkhartishvili, E\n\nChu, DK\n\nCingi, C\n\nColgan, E\n\nde Sousa, JC\n\nCourbis, AL\n\nCustovic, A\n\nCvetkosvki, B\n\nD'Amato, G\n\nda Silva, J\n\nDantas, C\n\nDokic, D\n\nDauvilliers, Y\n\nDedeu, A\n\nDe Feo, G\n\nDevillier, P\n\nDi Capua, S\n\nDykewickz, M\n\nDubakiene, R\n\nEbisawa, M\n\nEl-Gamal, Y\n\nEller, E\n\nEmuzyte, R\n\nFarrell, J\n\nFink-Wagner, A\n\nFiocchi, A\n\nFontaine, JF\n\nGemicioğlu, B\n\nSchmid-Grendelmeir, P\n\nGamkrelidze, A\n\nGarcia-Aymerich, J\n\nGomez, M\n\nGonzález Diaz, S\n\nGotua, M\n\nGuldemond, NA\n\nGuzmán, MA\n\nHajjam, J\n\nO'B Hourihane, J\n\nHumbert, M\n\nIaccarino, G\n\nIerodiakonou, D\n\nIllario, M\n\nIvancevich, JC\n\nJoos, G\n\nJung, KS\n\nJutel, M\n\nKaidashev, I\n\nKalayci, O\n\nKardas, P\n\nKeil, T\n\nKhaitov, M\n\nKhaltaev, N\n\nKleine-Tebbe, J\n\nKowalski, ML\n\nKritikos, V\n\nKull, I\n\nLeonardini, L\n\nLieberman, P\n\nLipworth, B\n\nLodrup Carlsen, KC\n\nLoureiro, CC\n\nLouis, R\n\nMair, A\n\nMarien, G\n\nMahboub, B\n\nMalva, J\n\nManning, P\n\nDe Manuel Keenoy, E\n\nMarshall, GD\n\nMasjedi, MR\n\nMaspero, JF\n\nMathieu-Dupas, E\n\nMatricardi, PM\n\nMelén, E\n\nMelo-Gomes, E\n\nMeltzer, EO\n\nMenditto, E\n\nMercier, J\n\nMiculinic, N\n\nMihaltan, F\n\nMilenkovic, B\n\nModa, G\n\nMogica-Martinez, MD\n\nMohammad, Y\n\nMontefort, S\n\nMonti, R\n\nMorais-Almeida, M\n\nMösges, R\n\nMünter, L\n\nMuraro, A\n\nMurray, R\n\nNaclerio, R\n\nNapoli, L\n\nNamazova-Baranova, L\n\nNeffen, H\n\nNekam, K\n\nNeou, A\n\nNovellino, E\n\nNyembue, D\n\nO'Hehir, R\n\nOhta, K\n\nOkubo, K\n\nOnorato, G\n\nOuedraogo, S\n\nPali-Schöll, I\n\nPalkonen, S\n\nPanzner, P\n\nPark, HS\n\nPépin, JL\n\nPereira, AM\n\nPfaar, O\n\nPaulino, E\n\nPhillips, J\n\nPicard, R\n\nPlavec, D\n\nPopov, TA\n\nPortejoie, F\n\nPrice, D\n\nProkopakis, EP\n\nPugin, B\n\nRaciborski, F\n\nRajabian-Söderlund, R\n\nReitsma, S\n\nRodo, X\n\nRomano, A\n\nRosario, N\n\nRottem, M\n\nRyan, D\n\nSalimäki, J\n\nSanchez-Borges, MM\n\nSisul, JC\n\nSolé, D\n\nSomekh, D\n\nSooronbaev, T\n\nSova, M\n\nSpranger, O\n\nStellato, C\n\nStelmach, R\n\nSuppli Ulrik, C\n\nThibaudon, M\n\nTo, T\n\nTodo-Bom, A\n\nTomazic, PV\n\nValero, AA\n\nValenta, R\n\nValentin-Rostan, M\n\nvan der Kleij, R\n\nVandenplas, O\n\nVezzani, G\n\nViart, F\n\nViegi, G\n\nWallace, D\n\nWagenmann, M\n\nWang, Y\n\nWaserman, S\n\nWickman, M\n\nWilliams, DM\n\nWong, G\n\nWroczynski, P\n\nYiallouros, PK\n\nYorgancioglu, A\n\nYusuf, OM\n\nZar, HJ\n\nZeng, S\n\nZernotti, M\n\nZhang, L\n\nZhong, NS\n\nZidarn, M\n\nARIA Study Group\n\nMASK Study Group\n\nBeiträge in Fachzeitschriften\nISI:000485072700001\n31516692.0\n10.1186/s13601-019-0279-2\nPMC6734297\nIn all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system into integrated care with organizational health literacy.\n As an example for chronic disease care, MASK (Mobile Airways Sentinel NetworK), a new project of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life ICPs centred around the patient with rhinitis, and using mHealth to monitor environmental exposure. Three aspects of care pathways are being developed: (i) Patient participation, health literacy and self-care through technology-assisted "patient activation", (ii) Implementation of care pathways by pharmacists and (iii) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) obtained through mobile technology. The EU and global political agendas are of great importance in supporting the digital transformation of health and care, and MASK has been recognized by DG Santé as a Good Practice in the field of digitally-enabled, integrated, person-centred care.\n In 20 years, ARIA has considerably evolved from the first multimorbidity guideline in respiratory diseases to the digital transformation of health and care with a strong political involvement.\n\nRoller-Wirnsberger, Regina\n\nTomazic, Peter Valentin\n\n\n"
}
]
}