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

ABSTRACT: 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.

SUBMITTER: Lu Y 

PROVIDER: S-EPMC3720123 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Lu Yi Y   Vitart Veronique V   Burdon Kathryn P KP   Khor Chiea Chuen CC   Bykhovskaya Yelena Y   Mirshahi Alireza A   Hewitt Alex W AW   Koehn Demelza D   Hysi Pirro G PG   Ramdas Wishal D WD   Zeller Tanja T   Vithana Eranga N EN   Cornes Belinda K BK   Tay Wan-Ting WT   Tai E Shyong ES   Cheng Ching-Yu CY   Liu Jianjun J   Foo Jia-Nee JN   Saw Seang Mei SM   Thorleifsson Gudmar G   Stefansson Kari K   Dimasi David P DP   Mills Richard A RA   Mountain Jenny J   Ang Wei W   Hoehn René R   Verhoeven Virginie J M VJ   Grus Franz F   Wolfs Roger R   Castagne Raphaële R   Lackner Karl J KJ   Springelkamp Henriët H   Yang Jian J   Jonasson Fridbert F   Leung Dexter Y L DY   Chen Li J LJ   Tham Clement C Y CC   Rudan Igor I   Vatavuk Zoran Z   Hayward Caroline C   Gibson Jane J   Cree Angela J AJ   MacLeod Alex A   Ennis Sarah S   Polasek Ozren O   Campbell Harry H   Wilson James F JF   Viswanathan Ananth C AC   Fleck Brian B   Li Xiaohui X   Siscovick David D   Taylor Kent D KD   Rotter Jerome I JI   Yazar Seyhan S   Ulmer Megan M   Li Jun J   Yaspan Brian L BL   Ozel Ayse B AB   Richards Julia E JE   Moroi Sayoko E SE   Haines Jonathan L JL   Kang Jae H JH   Pasquale Louis R LR   Allingham R Rand RR   Ashley-Koch Allison A   Mitchell Paul P   Wang Jie Jin JJ   Wright Alan F AF   Pennell Craig C   Spector Timothy D TD   Young Terri L TL   Klaver Caroline C W CC   Martin Nicholas G NG   Montgomery Grant W GW   Anderson Michael G MG   Aung Tin T   Willoughby Colin E CE   Wiggs Janey L JL   Pang Chi P CP   Thorsteinsdottir Unnur U   Lotery Andrew J AJ   Hammond Christopher J CJ   van Duijn Cornelia M CM   Hauser Michael A MA   Rabinowitz Yaron S YS   Pfeiffer Norbert N   Mackey David A DA   Craig Jamie E JE   Macgregor Stuart S   Wong Tien Y TY  

Nature genetics 20130106 2

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% conf  ...[more]

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