Genome-wide Meta-Analyses Of Multi-Ethnic Cohorts Identify Multiple New Susceptibility Loci For Refractive Error And Myopia

Abstract

Purpose: Refractive error is the most common eye disorder worldwide, and a prominent cause of blindness. Myopia affects over 30% of Caucasian populations, and up to 80% of Asians. We aimed to identify multiple genetic loci that explain the genetic architecture of refractive error.

Methods: The Consortium for Refractive Error and Myopia (CREAM) conducted genome-wide meta-analyses including 37,382 individuals from 27 Caucasian studies, and 8,376 from 5 Asian cohorts. Identified variants were used for genetic risk score assessment.

Results: We identified 16 new loci for refractive error in Caucasians, of which 10 were shared with Asians. Combined analysis revealed 8 additional new loci. The new loci include genes with function in neurotransmission (GRIA4), ion channels (KCNQ5), retinoic acid metabolism (RDH5), extracellular matrix remodeling (LAMA2, BMP2), and eye development (SIX6, PRSS56). We also confirmed previously reported associations with GJD2 (top SNP rs524952; P_combined=1.44x10^-15) and RASGRF1. Risk score analysis using associated SNPs showed a ten-fold increased risk of myopia for subjects with the highest genetic load.

Conclusions: Our results, accumulated across independent studies from four continents, considerably advance understanding of mechanisms involved in refractive error and myopia.

Keywords: 605 myopia • 677 refractive error development • 539 genetics