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


Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Lu, Y; Vitart, V; Burdon, KP; Khor, CC; Bykhovskaya, Y; Mirshahi, A; Hewitt, AW; Koehn, D; Hysi, PG; Ramdas, WD; Zeller, T; Vithana, EN; Cornes, BK; Tay, W-T; Tai, ES; Cheng, C-Y; Liu, J; Foo, J-N; Saw, SM; Thorleifsson, G; Stefansson, K; Dimasi, DP; Mills, RA; Mountain, J; Ang, W; Hoehn, R; Verhoeven, VJM; Grus, F; Wolfs, R; Castagne, R; Lackner, KJ; Springelkamp, H; Yang, J; Jonasson, F; Leung, DYL; Chen, LJ; Tham, CCY; Rudan, I; Vatavuk, Z; Hayward, C; Gibson, J; Cree, AJ; MacLeod, A; Ennis, S; Polasek, O; Campbell, H; Wilson, JF; Viswanathan, AC; Fleck, B; Li, X; Siscovick, D; Taylor, KD; Rotter, JI; Yazar, S; Ulmer, M; Li, J; Yaspan, BL; Ozel, AB; Richards, JE; Moroi, SE; Haines, JL; Kang, JH; Pasquale, LR; Allingham, RR; Ashley-Koch, A; NEIGHBOR Consortium, ; Mitchell, P; Wang, JJ; Wright, AF; Pennell, C; Spector, TD; Young, TL; Klaver, CCW; Martin, NG; Montgomery, GW; Anderson, MG; Aung, T; Willoughby, CE; Wiggs, JL; Pang, CP; Thorsteinsdottir, U; Lotery, AJ; Hammond, CJ; van Duijn, CM; Hauser, MA; Rabinowitz, YS; Pfeiffer, N; Mackey, DA; Craig, JE; Macgregor, S; Wong, TY

Published Date

  • February 2013

Published In

Volume / Issue

  • 45 / 2

Start / End Page

  • 155 - 163

PubMed ID

  • 23291589

Pubmed Central ID

  • 23291589

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.2506


  • eng

Conference Location

  • United States