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

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

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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.

Bibliographical data

Original languageEnglish
ISSN1061-4036
DOIs
Publication statusPublished - 02.2013
PubMed 23291589