Yang, B.B.YangZhou, W.W.ZhouJiao, J.J.JiaoNielsen, J.B.J.B.NielsenMathis, M.R.M.R.MathisHeydarpour, M.M.HeydarpourLettre, G.G.LettreFolkersen, L.L.FolkersenPrakash, S.S.PrakashSchurmann, C.C.SchurmannFritsche, L.L.FritscheFarnum, G.A.G.A.FarnumLin, M.M.LinOthman, M.M.OthmanHornsby, W.W.HornsbyDriscoll, A.A.DriscollLevasseur, A.A.LevasseurThomas, M.M.ThomasFarhat, L.L.FarhatDub\'e, M.-P.M.-P.Dub\'eIsselbacher, E.M.E.M.IsselbacherFranco-Cereceda, A.A.Franco-CerecedaGuo, D.-C.D.-C.GuoBottinger, E.P.E.P.BottingerDeeb, G.M.G.M.DeebBooher, A.A.BooherKheterpal, S.S.KheterpalChen, Y.E.Y.E.ChenKang, H.M.H.M.KangKitzman, J.J.KitzmanCordell, H.J.H.J.CordellKeavney, B.D.B.D.KeavneyGoodship, J.A.J.A.GoodshipGanesh, S.K.S.K.GaneshAbecasis, G.G.AbecasisEagle, K.A.K.A.EagleBoyle, A.P.A.P.BoyleLoos, R.J.F.R.J.F.LoosEriksson, P.P.ErikssonTardif, J.-C.J.-C.TardifBrummett, C.M.C.M.BrummettMilewicz, D.M.D.M.MilewiczBody, S.C.S.C.BodyWiller, C.J.C.J.Willer2024-10-142024-10-142017https://knowledge.hpi.de/handle/123456789/3105\textcopyright The Author(s) 2017. Bicuspid aortic valve (BAV) is a heritable congenital heart defect and an important risk factor for valvulopathy and aortopathy. Here we report a genome-wide association scan of 466 BAV cases and 4,660 age, sex and ethnicity-matched controls with replication in up to 1,326 cases and 8,103 controls. We identify association with a noncoding variant 151 kb from the gene encoding the cardiac-specific transcription factor, GATA4, and near-significance for p.Ser377Gly in GATA4. GATA4 was interrupted by CRISPR-Cas9 in induced pluripotent stem cells from healthy donors. The disruption of GATA4 significantly impaired the transition from endothelial cells into mesenchymal cells, a critical step in heart valve development.article