Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract

Commun Biol. 2020 Dec 11;3(1):755. doi: 10.1038/s42003-020-01421-2.

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.

Publication types

  • Meta-Analysis

MeSH terms

  • Alleles
  • Cataract / diagnosis
  • Cataract / etiology*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide
  • SOXB1 Transcription Factors / genetics*

Substances

  • SOX2 protein, human
  • SOXB1 Transcription Factors

Supplementary concepts

  • Cataract, Age-Related Nuclear