Longevity & AgingShared Genes Link Telomere Length to Heart Disease Risk
Researchers performed a comprehensive genome-wide pleiotropic analysis using large GWAS datasets to map the shared genetic architecture between leukocyte telomere length (LTL) and six major cardiovascular diseases (CVDs): atrial fibrillation, coronary artery disease, venous thromboembolism, heart failure, peripheral artery disease, and stroke. They identified 248 pleiotropic loci and confirmed 22 with strong colocalization evidence. Key shared genes included SH2B3, ALDH2, ACAD10, and SERPINF1. Mendelian randomization supported a causal link between shorter LTL and coronary artery disease. Proteome-wide Mendelian randomization validated SH2B3 as a potential therapeutic target. Functional pathway analysis implicated DNA biosynthesis and telomere maintenance mechanisms as central to the LTL–CVD relationship.
