Shared genetic architecture underlying cataract and cardiovascular disease: insights from multi-omics analyses

Shared genetic architecture underlying cataract and cardiovascular disease: insights from multi-omics analyses. Download PDF Abstract Cataract and cardiovascular disease (CVD) are prevalent age-related disorders with overlapping risk factors. While epidemiological associations are established, the shared genetic mechanisms underlying their comorbidity remain largely unexplored.

We performed a comprehensive genome-wide investigation integrating large-scale GWAS summary statistics for age-related cataract and four major CVDs (coronary artery disease, atrial fibrillation, heart failure, and myocardial infarction). Using multi-omics approaches including PLACO, MAGMA, SMR, and colocalization, we identified pleiotropic loci, credible genes, and evaluated their functional relevance. Pathway and gene-set enrichment analyses were conducted to elucidate the underlying biological mechanisms.

Significant genetic correlations were found for cataract with AF, CAD, and HF (LDSC and HDL, Bonferroni-corrected P < 0.0125); MI showed method-dependent significance (LDSC P = 0.021, HDL P = 1.71 × 10 −4). PLACO identified 924 shared SNPs mapped to 79 loci, of which 12 showed solid colocalization (PP.H4 > 0.8). MAGMA gene-set enrichment revealed pathways related to lipid metabolism, oxidative stress, and vascular development.

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