Genome-wide trans-ancestry meta-analysis identifies new susceptibility loci for age-related cortical cataract

Abstract

Purpose : Age-related cataract is a leading cause of visual impairment worldwide, especially in developing countries with limited access to cataract surgery. Cortical cataract is the second most prevalent type of age-related cataract, yet knowledge about its genetic etiology is lacking. We aimed to identify genetic variants influencing age-related cortical cataract.

Methods : We conducted a meta-analysis of genome-wide association studies (GWAS) for age-related cortical cataract, involving 9,055 individuals from 5 cohorts of European ancestry and 7,987 from 6 Asian cohorts. Study individuals were genotyped using either Illumina or Affymetrix platforms. After stringent quality controls, genotype data in each cohort were imputed to the 1000 Genomes reference panel. Severity of cortical lens opacity was measured based on lens photos according established protocols. The phenotype data were rank transformed and normalized before analysis. The genotype and phenotype association was assessed using linear regression analysis under an additive effect model, adjusting for age, gender and principal components. Meta-analysis was conducted under an inverse-variance-weighted fixed-effect model and two random-effects models (DerSimonian-Laird and Han-Eskin).

Results : The combined analysis of both Asian and Caucasian cohorts revealed one genome-wide significant locus and two suggestive susceptibility loci for cortical cataract with low cross-cohort heterogeneity. The most significant locus influencing cortical cataract was observed at chromosome 20q12 (p = 8.4 × 10^–10), followed by two loci at chromosome 8q11 (p = 7.3 × 10^–8) and 3q26 (p = 1.3 × 10^–7). Earlier studies showed that genes at these loci are expressed in ocular tissue and/or involved in development of the eye.

Conclusions : Our study is the first GWAS on age-related cortical cataract. The results yield insights at the gene level for the pathogenesis of age-related cortical cataract.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.