Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus.
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 None., 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.
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.