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 (h2 = 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.
Highlights
Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide
Given the potential of appropriately powered genetic studies to reveal aetiologies and pathways of age-related nuclear cataract (ARNC), we aimed to identify additional genomic regions associated with the susceptibility to ARNC via a meta-analysis of genomewide association studies (GWAS) of 12 well-phenotyped studies from the International Cataract Genetics Consortium
The results suggest a strong link of ARNC with genes linked to congenital cataract and eye development, as well as and the importance of common genetic variants in maintaining crystalline lens integrity during ageing
Summary
Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. 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. Genomewide association studies (GWAS) have not been very successful in the identifying common genetic variants for age-related cataract, partly due to the difficulties in objectively phenotyping ARNC. The only reported GWAS of ARNC with objective phenotyping via lens photos and detailed cataract grading was done in Asian cohorts, where two genetic loci (CRYAA, KCNAB1) were found associated with ARNC13. The results suggest a strong link of ARNC with genes linked to congenital cataract and eye development, as well as and the importance of common genetic variants in maintaining crystalline lens integrity during ageing
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