Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract.

Abstract

Age-related cataract is a leading cause of blindness worldwide, especially in developing countries where access to cataract surgery remains limited. Previous linkage and candidate gene studies suggested genetic influences on age-related nuclear cataract but few genetic markers have been identified thus far. We conducted genome-wide association studies on 4569 Asians (including 2369 Malays and 2200 Indians), and replicated our analysis in 2481 Chinese from two independent cohorts (1768 Chinese in Singapore and 803 Chinese in Beijing). We confirmed two genome-wide significant loci for nuclear cataract in the combined meta-analysis of four cohorts (n = 7140). The first locus was at chromosome 3q25.31 in KCNAB1 (rs7615568, fixed-effect Pmeta = 2.30 × 10(-8); random-effect Pmeta = 1.08 × 10(-8)). The second locus was at chromosome 21 in the proximity of CRYAA (rs11911275, fixed-effect Pmeta = 2.77 × 10(-8); random-effect Pmeta = 1.98 × 10(-9)), a major protein component of eye lens. The findings were further supported by up-regulation and down-regulation of KCNAB1 and CRYAA in human lens capsule, respectively, as the severity of nuclear cataract increases. The results offer additional insights into the pathogenesis of nuclear cataract in Asians.

• Authors: Jiemin Liao, Xinyi Su, Peng Chen, Xu Wang, Liang Xu, Xiang Li, Lennard Thean, Clement Tan, Ava G Tan, Wan-Ting Tay, Gyungah Jun, Yingfeng Zheng, Merwyn Chew, Ya Xing Wang, Queenie S Tan, Veluchamy A Barathi, Barbara E Klein, Seang-Mei Saw, Eranga N Vithana, E-Shyong Tai, Sudha K Iyengar, Paul Mitchell, Chiea-Chuen Khor, Tin Aung, Jie Jin Wang, Jost B Jonas, Yik-Ying Teo, Tien Yin Wong, Ching-Yu Cheng
• Journal: Human molecular genetics (Hum Mol Genet) Vol. 23 Issue 22 Pg. 6119-28 (Nov 15 2014) ISSN: 1460-2083 [Electronic] England
• PMID: 24951543 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• CRYAA protein, human
• Crystallins
• KCNAB1 protein, human
• Kv1.3 Potassium Channel

Topics

• Aged
• Asian People (ethnology, genetics)
• Cataract (ethnology, genetics)
• Cohort Studies
• Crystallins (genetics)
• Female
• Genetic Predisposition to Disease (ethnology)
• Genome-Wide Association Study
• Genotype
• Humans
• Kv1.3 Potassium Channel (genetics)
• Male
• Middle Aged