A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure.
A large multi-ethnic genome-wide association study identifies novel genetic loci for intraocular pressure.
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DOI：
10.1038/s41467-017-01913-6
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发表时间：
2017-12-13
影响因子：
16.6
通讯作者：
Jorgenson E
中科院分区：
文献类型：
--
作者：
Choquet H;Thai KK;Yin J;Hoffmann TJ;Kvale MN;Banda Y;Schaefer C;Risch N;Nair KS;Melles R;Jorgenson E
眼内压 (IOP) 升高是青光眼的主要危险因素，青光眼是导致失明的主要原因。 IOP 遗传力估计高达 67%，迄今为止仅报道了 11 个 IOP 基因座，占 IOP 变异性的 1.5%。在这里，我们对 69,756 名未经治疗的欧洲、拉丁裔、亚洲和非洲血统个体进行了 IOP 的全基因组关联研究。通过电子健康记录收集了多个纵向 IOP 测量值，总共包含 356,987 个测量值。我们鉴定了 47 个全基因组显着的 IOP 相关位点 (P < 5 × 10−8)；在对 37,930 名欧洲和亚洲血统个体进行的外部全基因组关联研究分析中，40 个新基因座中，有 14 个具有 Bonferroni 显着性重复。我们在我们的发现样本中进一步研究了它们对青光眼风险的影响。使用电子健康记录中的纵向 IOP 测量可以提高我们识别新变异的能力，这些变异共同解释了 3.7% 的 IOP 变异。眼内压 (IOP) 是青光眼的主要危险因素。在这里，Choquet 和合著者对 69,756 名个体进行了重复 IOP 测量的多种族全基因组关联研究，并确定了 40 个新基因座，其中 36 个在青光眼中显示出方向一致的效应。
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, a leading cause of blindness. IOP heritability has been estimated to up to 67%, and to date only 11 IOP loci have been reported, accounting for 1.5% of IOP variability. Here, we conduct a genome-wide association study of IOP in 69,756 untreated individuals of European, Latino, Asian, and African ancestry. Multiple longitudinal IOP measurements were collected through electronic health records and, in total, 356,987 measurements were included. We identify 47 genome-wide significant IOP-associated loci (P < 5 × 10−8); of the 40 novel loci, 14 replicate at Bonferroni significance in an external genome-wide association study analysis of 37,930 individuals of European and Asian descent. We further examine their effect on the risk of glaucoma within our discovery sample. Using longitudinal IOP measurements from electronic health records improves our power to identify new variants, which together explain 3.7% of IOP variation. Intraocular pressure (IOP) is a major risk factor for glaucoma. Here, Choquet and co-authors perform a multi-ethnic genome-wide association study of repeat IOP measurements in 69,756 individuals and identify 40 novel loci, 36 of which show directionally consistent effects in glaucoma.
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影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
30.8
作者：
Gharahkhani, Puya;Burdon, Kathryn P.;Fogarty, Rhys;Sharma, Shiwani;Hewitt, Alex W.;Martin, Sarah;Law, Matthew H.;Cremin, Katie;Bailey, Jessica N. Cooke;Loomis, Stephanie J.;Pasquale, Louis R.;Haines, Jonathan L.;Hauser, Michael A.;Viswanathan, Ananth C.;McGuffin, Peter;Topouzis, Fotis;Foster, Paul J.;Graham, Stuart L.;Casson, Robert J.;Chehade, Mark;White, Andrew J.;Zhou, Tiger;Souzeau, Emmanuelle;Landers, John;Fitzgerald, Jude T.;Klebe, Sonja;Ruddle, Jonathan B.;Goldberg, Ivan;Healey, Paul R.;Mills, Richard A.;Wang, Jie Jin;Montgomery, Grant W.;Martin, Nicholas G.;Radford-Smith, Graham;Whiteman, David C.;Brown, Matthew A.;Wiggs, Janey L.;Mackey, David A.;Mitchell, Paul;MacGregor, Stuart;Craig, Jamie E.
通讯作者：
Craig, Jamie E.
影响因子：
30.8
作者：
Fritsche, Lars G.;Chen, Wei;Schu, Matthew;Yaspan, Brian L.;Yu, Yi;Thorleifsson, Gudmar;Zack, Donald J.;Arakawa, Satoshi;Cipriani, Valentina;Ripke, Stephan;Igo, Robert P., Jr.;Buitendijk, Gabrielle H. S.;Sim, Xueling;Weeks, Daniel E.;Guymer, Robyn H.;Merriam, Joanna E.;Francis, Peter J.;Hannum, Gregory;Agarwal, Anita;Armbrecht, Ana Maria;Audo, Isabelle;Aung, Tin;Barile, Gaetano R.;Benchaboune, Mustapha;Bird, Alan C.;Bishop, Paul N.;Branham, Kari E.;Brooks, Matthew;Brucker, Alexander J.;Cade, William H.;Cain, Melinda S.;Campochiaroll, Peter A.;Chan, Chi-Chao;Cheng, Ching-Yu;Chew, Emily Y.;Chin, Kimberly A.;Chowers, Itay;Clayton, David G.;Cojocaru, Radu;Conley, Yvette P.;Cornes, Belinda K.;Daly, Mark J.;Dhillon, Baljean;Edwards, Albert;Evangelou, Evangelos;Fagemess, Jesen;Ferreyra, Henry A.;Friedman, James S.;Geirsdottir, Asbjorg;George, Ronnie J.;Gieger, Christian;Gupta, Neel;Hagstrom, Stephanie A.;Harding, Simon P.;Haritoglou, Christos;Heckenlively, John R.;Hoz, Frank G.;Hughes, Guy;Ioannidis, John P. A.;Ishibashi, Tatsuro;Joseph, Peronne;Jun, Gyungah;Kamatani, Yoichiro;Katsanis, Nicholas;Keilhauer, Claudia N.;Khan, Jane C.;Kim, Ivana K.;Kiyohara, Yutaka;Klein, Barbara E. K.;Klein, Ronald;Kovach, Jaclyn L.;Kozak, Igor;Lee, Clara J.;Lee, Kristine E.;Lichtner, Peter;Lotery, Andrew J.;Meitinger, Thomas;Mitchell, Paul;Mohand-Saied, Saddek;Moore, Anthony T.;Morgan, Denise J.;Morrison, Margaux A.;Myers, Chelsea E.;Naj, Adam C.;Nakamura, Yusuke;Okada, Yukinori;Orlin, Anton;Ortube, M. Carolina;Othman, Mohammad I.;Pappas, Chris;Park, Kyu Hyung;Pauer, Gayle J. T.;Peachey, Neal S.;Poch, Olivier;Priya, Rinki Ratna;Reynolds, Robyn;Richardson, Andrea J.;Ripp, Raymond;Rudolph, Guenther;Ryu, Euijung;Sahel, Jose-Alain;Schaumberg, Debra A.;Scholl, Hendrik P. N.;Schwartz, Stephen G.;Scott, William K.;Shahid, Humma;Sigurdsson, Haraldur;Silvestri, Giuliana;Sivakumaran, Theru A.;Smith, R. Theodore;Sobrin, Lucia;Souied, Eric H.;Stambolian, Dwight E.;Stefansson, Hreinn;Sturgill-Short, Gwen M.;Takahashi, Atsushi;Tosakulwong, Nirubol;Truitt, Barbara J.;Tsironi, Evangelia E.;Uitterlinden, Andre G.;van Duijn, Cornelia M.;Vijaya, Lingam;Vingerling, Johannes R.;Vithana, Eranga N.;Webster, Andrew R.;Wichmann, H-Erich;Winkler, Thomas W.;Wong, Tien Y.;Wright, Alan F.;Zelenika, Diana;Zhang, Ming;Zhao, Ling;Zhang, Kang;Klein, Michael L.;Hageman, Gregory S.;Lathrop, G. Mark;Stefansson, Kari;Allikmets, Rando;Baird, Paul N.;Gorin, Michael B.;Wang, Jie Jin;Klaver, Caroline C. W.;Seddon, Johanna M.;Pericak-Vance, Margaret A.;Iyengar, Sudha K.;Yates, John R. W.;Swaroop, Anand;Weber, Bernhard H. F.;Kubo, Michiaki;DeAngelis, Margaret M.;Leveillard, Thierry;Thorsteinsdottir, Unnur;Haines, Jonathan L.;Farrer, Lindsay A.;Heid, Iris M.;Abecasis, Goncalo R.
通讯作者：
Abecasis, Goncalo R.
影响因子：
3.5
作者：
Blue Mountains Eye Study (BMES);Wellcome Trust Case Control Consortium 2 (WTCCC2)
通讯作者：
Wellcome Trust Case Control Consortium 2 (WTCCC2)
影响因子：
4.4
作者：
D'haene, Barbara;Meire, Francoise;De Baere, Elfride
通讯作者：
De Baere, Elfride