Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract
Ekaterina Yonova‐Doing, Wanting Zhao, Robert P. Igo, Chaolong Wang, Periasamy Sundaresan, Kristine E. Lee, Gyungah Jun, Alexessander Couto Alves, Xiaoran Chai, Anita Sook Yee Chan, Mei Lee, Allan Fong, Ava Grace Tan, Chiea Chuen Khor, Emily Y. Chew, Pirro G. Hysi, Qiao Fan, Jacqueline Chua, Jaeyoon Chung, Jiemin Liao, Johanna Maria Colijn, Kathryn P. Burdon, Lars G. Fritsche, Maria Swift, Maryam Hazly Hilmy, Miao Ling Chee, Milly S. Tedja, Pieter W. M. Bonnemaijer, Preeti Gupta, Queenie Shu Woon Tan, Zheng Li, Eranga N. Vithana, Ravilla D. Ravindran, Soon-Phaik Chee, Yuan Shi, Wenting Liu, Xinyi Su, Xueling Sim, Yang Shen, Ya Xing Wang, Hengtong Li, Yih Chung Tham, Yik Ying Teo, Tin Aung, Kerrin S. Small, Paul Mitchell, Jost B. Jonas, Tien Yin Wong, Astrid Fletcher, Caroline C. W. Klaver, Barbara E.K. Klein, Jie Jin Wang, Sudha K. Iyengar, Christopher J. Hammond, Ching‐Yu Cheng
Abstract
Abstract Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable ( h 2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10 −16 ) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10 −19 ), TMPRSS5 (rs4936279, P = 2.5 × 10 −10 ), LINC01412 (rs16823886, P = 1.3 × 10 −9 ), GLTSCR1 (rs1005911, P = 9.8 × 10 −9 ), and COMMD1 (rs62149908, P = 1.2 × 10 −8 ). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye.