Association of the SIX6 locus with primary open angle glaucoma in southern Chinese and Japanese. (March 2019)

• Record Type: Journal Article
• Authors: Rong, Shi Song; Lu, Shi Yao; Matsushita, Kenji; Huang, Chukai; Leung, Christopher K.S.; Kawashima, Rumi; Usui, Shinichi; Tam, Pancy O.S.; Young, Alvin L.; Tsujikawa, Motokazu; Zhang, Mingzhi; Nishida, Kohji; Wiggs, Janey L.; Tham, Clement C.; Pang, Chi Pui; Chen, Li Jia
• Is Part Of: Experimental eye research. Volume 180(2019)
• Page Start: 129
• Page End: 136
• Publication Date: 2019-03
• Subjects: SIX6 -- Glaucoma -- POAG -- Association -- Genetics; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2018.12.014
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: The purpose of the study was to evaluate the association profiles of the SIX6 locus with primary open-angle glaucoma (POAG) in southern Chinese and Japanese. In this study, we tested single marker and haplotype-based associations of 11 tagging single nucleotide polymorphisms (SNPs) covering the SIX6 locus with POAG in a Hong Kong Chinese cohort (N = 1402). A novel SNP (i.e., rs12436579) and two SNPs (i.e., rs33912345 and rs10483727) from previous genome-wide association studies were further tested in a Chinese cohort from Shantou (N = 888) and a Japanese cohort from Osaka (N = 463). Results from the three cohorts were meta-analysed using a random-effect model. We found rs12436579, which has not been previously reported, was associated with POAG in Hong Kong and Shantou Chinese (Pcombined = 4.3 × 10 −5, OR = 0.72, I 2 = 0). Additionally, we replicated the association of one known SNP, rs33912345 (Pcombined = 0.0061, OR = 0.69, I 2 = 45%), with POAG in the Chinese cohorts but not in the Japanese cohort (P > 0.6). Another known SNP, rs10483727, was nominally associated with POAG in the two Chinese cohorts (Pcombined = 0.017, OR = 0.70, I 2 = 53%). All these three SNPs were significantly associated with POAG when the three cohorts were combined in meta-analysis (Pcombined <0.005). Furthermore, two haplotypes, C-C (Pcombined = 1.13 × 10 −5, OR = 1.41, I 2 = 0) and A-A (Pcombined = 0.045, OR = 0.68, I 2 = 70%), defined by rs33912345-rs12436579 were associated with POAG in Chinese but not in Japanese. In conclusion, this study confirmed the association between two GWAS SNPs in SIX6 (rs33912345 and rs10483727) and POAG. Also, a SNP, rs12436579, not associated with POAG before, was found to be associated with POAG in Chinese. Further studies are warranted to elucidate the role of this novel SNP in POAG. Highlights: Validation of reported association between the SIX6 SNPs and POAG. Identification of a novel SNP rs12436579 associated with POAG in Southern Chinese. Haplotype rs33912345-rs12436579 had a stronger association than single SNP. Different association patterns of SIX6 with POAG between Chinese and Japanese.