Genome-wide association study identifies a new genetic locus at 2q36.3 for polypoidal choroidal vasculopathy in East Asians: The GAMA consortium

Abstract

Purpose : Polypoidal choroidal vasculopathy (PCV) is the most common subtype of age-related macular degeneration (AMD) in East Asians. Genome-wide association studies (GWASs) have identified at least 30 genetic variants for AMD. However, it remains unclear whether there is any unique genetic variation for PCV. In this study, we aim to identify susceptibility loci unique to PCV in East Asian populations.

Methods : We conducted a GWAS of 1,062 PCV cases and 1,152 typical noevascular AMD (tAMD) cases versus 5,275 non-AMD controls, comprising individuals of East Asian ancestry recruited in the Genetics of AMD in Asians (GAMA) Consortium. Genetic variants were genotyped using the Illumina HumanOmniExpress bead chips and imputed with multi-ethnic 1000 genome data as reference panels. For the replication, we genotyped a total of 895 PCV cases, 721 tAMD cases and 5,734 non-AMD controls from 3 independent sample collections in East Asians.

Results : At the discovery stage, three loci showed genome-wide significant association with PCV (P < 5.0 × 10^-8), including known loci of ARMS2 (rs11200634, P =9.97 x 10^-14) and CFH (rs514591, P = 1.45 x 10^-26), and a novel locus at 2q36.3 (odds ratio [OR] = 1.45, P = 2.88 × 10^-8). We replicate the 2q36.3 regions in three independent sample collections (OR = 1.26, P = 3.35×10^-4; overall P = 1.18 × 10^-10). For tAMD, the association at the 2q36.3 locus was marginal (overall OR = 1.18; P = 1.02×10^-3), with smaller effect size compared to PCV (P_dif = 0.048). The new genetic locus is involved in the structure of basement membrane in RPE and choriocapillaris.

Conclusions : We found a new genetic locus associated with PCV susceptibility and this locus is more closely involved in the pathogenesis of PCV than that of tAMD.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.