Association of the SIX1-SIX6 Locus with Primary Open-angle Glaucoma in Chinese and Japanese

Abstract

Purpose : To evaluate the association of the SIX1-SIX6 locus with primary open-angle glaucoma (POAG) in Chinese and Japanese.

Methods : Two Chinese cohorts from Hong Kong and Shantou, respectively, and one Japanese cohort from Osaka, totalling 2528 subjects (1223 POAG patients vs. 1305 controls) were recruited in this study. Thirteen single-nucleotide polymorphisms (SNPs), including 11 haplotype-tagging SNPs covering the entire SIX1-SIX6 locus and 2 SNPs from previous genome-wide association studies (GWAS, rs33912345 and rs10483727) were genotyped.

Results : In univariate association analysis, we identified a new SNP (rs12436579) to be associated with POAG (P=0.0064) in the Hong Kong cohort. One SNP reported by GWAS (rs33912345) showed a borderline association (P=0.067). In the replication analysis, these 2 SNPs were associated with POAG in the Shantou cohort (P<0.015), with the odds ratios (ORs) pointing to the same direction as that in the Hong Kong cohort. In the Osaka cohort, these 2 SNPs did not showed statistical significance (P>0.19), although their ORs were towards the same direction as that in the Hong Kong and Shantou cohorts. In the meta-analysis combining the 3 cohorts, the associations of these 2 SNPs were significant with low inter-cohort heterogeneities (rs33912345: P_meta=0.0016, OR=0.78, I²=0; rs12436579: P_meta=0.00075, OR=0.79, I²=10%).

Conclusions : This study confirmed the association of the SIX1-SIX6 locus with POAG in Chinese and Japanese, and identified a new tagging SNP (rs12436579) for POAG.

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