Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error.

Publications // Young Lab // Mar 19 2020

PubMed ID: 32193507

Author(s): Fan Q, Pozarickij A, Tan NYQ, Guo X, Verhoeven VJM, Vitart V, Guggenheim JA, Miyake M, Tideman JWL, Khawaja AP, Zhang L, MacGregor S, Höhn R, Chen P, Biino G, Wedenoja J, Saffari SE, Tedja MS, Xie J, Lanca C, Wang YX, Sahebjada S, Mazur J, Mirshahi A, Martin NG, Yazar S, Pennell CE, Yap M, Haarman AEG, Enthoven CA, Polling J; Consortium for Refractive Error and Myopia (CREAM); UK Biobank Eye and Vision Consortium, Hewitt AW, Jaddoe VWV, van Duijn CM, Hayward C, Polasek O, Tai ES, Yoshikatsu H, Hysi PG, Young TL, Tsujikawa A, Wang JJ, Mitchell P, Pfeiffer N, Pärssinen O, Foster PJ, Fossarello M, Yip SP, Williams C, Hammond CJ, Jonas JB, He M, Mackey DA, Wong TY, Klaver CCW, Saw SM, Baird PN, Cheng CY. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error. Commun Biol. 2020 Mar 19;3(1):133. doi: 10.1038/s42003-020-0802-y. PMID 32193507

Journal: Communications Biology, Volume 3, Issue 1, 03 2020

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia – a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.