Common Variants In Sox-2 And Congenital Cataract Genes Contribute To Age-Related Nuclear Cataract

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=2.8x10(-16)) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P=1.7x10(-19)), TMPRSS5 (rs4936279, P=2.5x10(-10)), LINC01412 (rs16823886, P=1.3x10(-9)), GLTSCR1 (rs1005911, P=9.8x10(-9)), and COMMD1 (rs62149908, P=1.2x10(-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. Here, the authors report a multi-ethnic genome wide association meta-analysis of 12 studies from the International Cataract Genetics Consortium. They find six new loci associated with age-related nuclear cataract, in addition to replicating the association at CRYAA, and suggest a strong genetic link between age-related nuclear and congenital cataracts.