Meta-analysis of genome-wide association studies on retinal nerve fber layer thickness in multi-ethnic Asians

Abstract

Purpose : Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by optic nerve degeneration. Retinal nerve fiber layer (RNFL) thickness measurement is an important clinical measurement used for diagnosis and monitoring of glaucoma. In this study, we conducted a meta-analysis of genome-wide association studies for RNFL in multi-ethnic Asian populations.

Methods : In this multi-ethnic meta-analysis, we enrolled 1,024 Malay, 1,406 Indian, 2,289 Chinese and 4,074 Japanese individuals, from 5 population-based studies across three countries, including Singapore Malay Eye Study, Singapore Indian Eye Study, Singapore Chinese Eye Study, Beijing Eye Study, and Nagahama Study. Peripapillary RNFL thickness was measured using spectral domain optical coherence tomography. Genome-wide genotyping was performed using Illumina Human610-Quad, OmniExpress, or HumanOmni2.5M arrays. Genotype imputation was performed using the 1000 Genomes Project as the reference panel. In each cohort, association analyses were first performed using linear regression model, with RNFL thickness as outcome, adjusting for age, gender axial length and the first 3 principal components of genetic ancestry. Fixed effect meta-analysis was then performed across study cohorts.

Results : We identified 3 genome-wide significant loci for average peripapillary RNFL thickness, including CDKN2B-AS1 (P = 5.96 x 10^-9), ATOH7 (P = 3.13 x 10^-8) and PBLD (P = 4.67 x 10^-8). These 3 loci were previously reported to be associated with vertical cup-disc ratio, another important optic nerve parameter for glaucoma assessment. In addition, CDKN2B-AS1 was also reported to be a risk locus for primary open-angle glaucoma.

Conclusions : We discovered 3 loci significantly associated with RNFL thickness in Asian populations. These findings may provide further insights into the genetic architecture of glaucoma.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.