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

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.

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

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