Nature genetics · 2013

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.

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Lu Yi, Vitart Veronique, Burdon Kathryn P, Khor Chiea Chuen, Bykhovskaya Yelena, Mirshahi Alireza, Hewitt Alex W, Koehn Demelza, Hysi Pirro G, Ramdas Wishal D, Zeller Tanja, Vithana Eranga N, Cornes Belinda K, Tay Wan-Ting, Tai E Shyong, Cheng Ching-Yu, Liu Jianjun, Foo Jia-Nee, Saw Seang Mei, Thorleifsson Gudmar, Stefansson Kari, Dimasi David P, Mills Richard A, Mountain Jenny, Ang Wei, Hoehn René, Verhoeven Virginie J M, Grus Franz, Wolfs Roger, Castagne Raphaële, Lackner Karl J, Springelkamp Henriët, Yang Jian, Jonasson Fridbert, Leung Dexter Y L, Chen Li J, Tham Clement C Y, Rudan Igor, Vatavuk Zoran, Hayward Caroline, Gibson Jane, Cree Angela J, MacLeod Alex, Ennis Sarah, Polasek Ozren, Campbell Harry, Wilson James F, Viswanathan Ananth C, Fleck Brian, Li Xiaohui, Siscovick David, Taylor Kent D, Rotter Jerome I, Yazar Seyhan, Ulmer Megan, Li Jun, Yaspan Brian L, Ozel Ayse B, Richards Julia E, Moroi Sayoko E, Haines Jonathan L, Kang Jae H, Pasquale Louis R, Allingham R Rand, Ashley-Koch Allison, NEIGHBOR Consortium, Mitchell Paul, Wang Jie Jin, Wright Alan F, Pennell Craig, Spector Timothy D, Young Terri L, Klaver Caroline C W, Martin Nicholas G, Montgomery Grant W, Anderson Michael G, Aung Tin, Willoughby Colin E, Wiggs Janey L, Pang Chi P, Thorsteinsdottir Unnur, Lotery Andrew J, Hammond Christopher J, van Duijn Cornelia M, Hauser Michael A, Rabinowitz Yaron S, Pfeiffer Norbert, Mackey David A, Craig Jamie E, Macgregor Stuart, Wong Tien Y

Аннотация

Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10(-8)). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4-1.88, P = 2.7 × 10(-10), and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29-1.68, P = 4.9 × 10(-9)). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10(-4); tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

Предметные рубрики MeSH

Asian People Cornea Corneal Pachymetry Fibronectins Forkhead Box Protein O1 Forkhead Transcription Factors Genetic Loci Genome-Wide Association Study Glaucoma Humans Keratoconus Microarray Analysis Odds Ratio Real-Time Polymerase Chain Reaction White People

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.

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Аннотация

Предметные рубрики MeSH