title: 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.
authors.affiliation: Queensland Institute of Medical Research, Statistical Genetics, Herston, Brisbane, Queensland, Australia.
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mesh_terms: D044466:Asian People / Q000235:genetics; D003315:Cornea / Q000033:anatomy & histology*; D063171:Corneal Pachymetry; D005353:Fibronectins / Q000235:genetics*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056426:Genetic Loci / Q000235:genetics*; D055106:Genome-Wide Association Study; D005901:Glaucoma / Q000235:genetics; D006801:Humans; D007640:Keratoconus / Q000235:genetics*; D046228:Microarray Analysis; D016017:Odds Ratio; D060888:Real-Time Polymerase Chain Reaction; D044465:White People / Q000235:genetics
chemical_list: C543006:FNDC3B protein, human; C085126:FOXO1 protein, human; D005353:Fibronectins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors