Abstract

Purpose: Purpose: Primary angle closure glaucoma (PACG) is a major form of glaucoma in Asia. We previously reported a genome-wide association study (GWAS) identifying three common genetic variants associated with PACG (Nature Genetics 2012; 44:1142-6). To further dissect the genetic architecture underling PACG susceptibility, we now expand the GWAS to include 3859 PACG cases and 15501 controls which included fresh samples from China, Japan, Singapore, and Vietnam.<br />

Methods: Methods: We freshly collected and genotyped a total of 2,005 PACG cases and 5,893 controls from China, Japan, Singapore, and Vietnam. Results from these fresh cases and controls were meta-analyzed with the original 1,854 PACG cases and 9,608 controls (Nature Genetics 2012; 44:1142-6), making the grand total of the discovery GWAS effort to comprise 3859 PACG cases and 15501 controls. Meta-analysis summarizing the results across all 9 genotyped cohorts was performed using fixed effects modeling weighted in an inverse-variance manner.<br />

Results: Results: We confirm strong association at PLEKHA7 rs11024102 (P = 1.4 x 10^-11), as well as at COL11A1 (P < 5 x 10^-8) in this new, expanded GWAS discovery collection. We also note strong association at two novel genetic loci. The first maps to Chromosome 7p (OR = 1.28, P = 9.6 x 10^-9), and the second maps to Chromosome 9q (OR = 1.20, P = 1.8 x 10^-9). We also note a significant excess of genetic markers surpassing P < 1 x 10^-6, suggesting that many of them could represent true positive associations with PACG.<br />

Conclusions: Conclusions: Our expanded GWAS conducted on 3,859 PACG cases and 15,501 controls clearly confirmed previous observations, and definitively identified at least two novel loci for PACG. Replication experiments for robust verification of these new findings are now underway. Our findings could potentially further increase current understanding on the disease mechanisms underlying PACG.