Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma
Chiea Chuen Khora b c✉, Tan Dod e, Hongyan Jiaf, Masakazu Nakanog, Ronnie Jacob Georgeh, Khaled K. Abu‐Ameroi j, Roopam Duveshk, Li Jia Chenl, Zheng Lib, Monisha Esther Nongpiurc e, Shamira Pererac e, Chunyan Qiaof, Hon Tym Wongm, Hiroshi Sakain o, Mônica Barbosa de Melop, Mei Leec e, Anita Sook Yee Chanc e, Azhany Yaakubq, Thi Lam Huong Daod, Yoko Ikedar, Rodolfo A. Perez-Grossmanns, Tomasz Żarnowskit, Alexander Clifford Dayu v w, Jost Bruno Jonasx, Pancy O. S. Taml, Tuan Anh Trand y, Humaira Ayubz, Farah Akhtaraa, Shazia Michealab, Paul Chewac and 199 others
- aDepartment of Biochemistry, National University of Singapore, Singapore
- bGenome Institute of Singapore, A-STAR, Singapore
- cSingapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke-National University of Singapore, Singapore
- dVietnam National Institute of Ophthalmology, Hanoi, Vietnam
- eSingapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke–National University of Singapore, Singapore
- fBeijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China
- gDepartment of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan
- hJadhavbhai Nathamal Singhvi Department of Glaucoma, Medical Research Foundation, Sankara Nethralaya, Chennai, India
- iDepartment of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
- j
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Abstract
Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

