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Eranga Nishanthie Vithana, Zheng Li, Baskaran Mani, Shamira A Perera, Jia Yu Koh, Tien Yin Wong, Chiea Chuen Khor, Ching-Yu Cheng, Tin Aung; . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):2547.
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© ARVO (1962-2015); The Authors (2016-present)
Primary open angle glaucoma (POAG) is a complex trait, for which genome-wide association studies (GWAS) have identified 10 disease risk loci (CAV1-CAV2, TMCO1, CDKN2B-AS1, SIX1-SIX6, an intergenic region on chromosome 8q22, ABCA1, GAS7, AFAP1, GMDS and PMM2). As these genetic loci were identified mostly from European ancestry populations, we analyzed all 10 loci in Chinese POAG subjects from Singapore to assess their transferability to individuals of Chinese ancestry.
We collected and genotyped a total of 1224 Chinese POAG cases and 2587 controls from Singapore. All cases were >40 years old and comprised of normal tension glaucoma (NTG) and high tension glaucoma (HTG). Genotyping was performed using the Illumina Human OmniExpress or Human610-Quad BeadChips. After sample and SNP quality control checks, 1023 POAG cases and 2406 controls remained for statistical analyses. The association between genotypes and POAG risk was assessed using logistic regression with additive effect models, adjusted for genetic principal components. We examined the association of lead and tagging SNPs in the 10 POAG loci with glaucoma. A p-value of 0.005 was set to account for the testing of 10 genetic loci using a Bonferroni correction.
The Chinese POAG cohort consisted of 294 cases with NTG and 722 with HTG. Of the 10 loci investigated only SNPs at CDKN2B-AS1, SIX1-SIX6, ABCA1, GMDS, GAS7 and PMM2 showed experimentally significant associations with POAG. The top associated SNPs were rs1063192 [G] in CDKN2B-AS1 (odds ratio [OR]=0.72, P= 3.83E-05), rs2164560 [C] in ABCA1 (OR=0.79, P= 4.91E-05), rs7759192 [A] in GMDS (OR=0.6826, P= 1.8E-04), rs12150284 [T] in GAS7 (OR=0.8194, P= 2.75E-04), rs3785176 [C] in PMM2 (OR=1.2, P= 3.41E-03) and rs10483727 [C] in SIX1-SIX6 (OR=0.8309, p=7.40E-3). AFAP1 SNP rs4478172 showed nominal association with POAG (OR= 0.8734, P=0.01305). Subgroup analysis indicated that association at CDKN2B-AS1 rs1063192 [G] was strongest in the NTG cohort (N=293) (OR=0.54, P= 2.31E-05), supporting previous findings in Caucasian and Japanese cohorts.
The recently identified ABCA1, AFAP1, GMDS, GAS7 and PMM2 loci were also associated with POAG in our Chinese cohort demonstrating them as robust POAG associations, with global implications.
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