Nature communications · 2018

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

СтатьяМетаанализНазвание и аннотация: Перевод в очереди

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Iglesias Adriana I, Mishra Aniket, Vitart Veronique, Bykhovskaya Yelena, Höhn René, Springelkamp Henriët, Cuellar-Partida Gabriel, Gharahkhani Puya, Bailey Jessica N Cooke, Willoughby Colin E, Li Xiaohui, Yazar Seyhan, Nag Abhishek, Khawaja Anthony P, Polašek Ozren, Siscovick David, Mitchell Paul, Tham Yih Chung, Haines Jonathan L, Kearns Lisa S, Hayward Caroline, Shi Yuan, van Leeuwen Elisabeth M, Taylor Kent D, Blue Mountains Eye Study—GWAS group, Bonnemaijer Pieter, Rotter Jerome I, Martin Nicholas G, Zeller Tanja, Mills Richard A, Souzeau Emmanuelle, Staffieri Sandra E, Jonas Jost B, Schmidtmann Irene, Boutin Thibaud, Kang Jae H, Lucas Sionne E M, Wong Tien Yin, Beutel Manfred E, Wilson James F, NEIGHBORHOOD Consortium, Wellcome Trust Case Control Consortium 2 (WTCCC2), Uitterlinden André G, Vithana Eranga N, Foster Paul J, Hysi Pirro G, Hewitt Alex W, Khor Chiea Chuen, Pasquale Louis R, Montgomery Grant W, Klaver Caroline C W, Aung Tin, Pfeiffer Norbert, Mackey David A, Hammond Christopher J, Cheng Ching-Yu, Craig Jamie E, Rabinowitz Yaron S, Wiggs Janey L, Burdon Kathryn P, van Duijn Cornelia M, MacGregor Stuart

Аннотация

Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10-5) but not between CCT and primary open-angle glaucoma (r = -0.17, P = 0.2). Our findings provide evidence for shared genetic influences between CCT and keratoconus, and implicate candidate genes acting in collagen and extracellular matrix regulation.

Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases.

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