Genome-wide Association Study of Cardiovascular Traits in 6142 Sardinians

National Institute On Aging

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Abstract

We identified 177, 156 and 121 independent loci (114, 97, 77 unreported previously) for QT, JT and QRS in multi-ancestry analyses (sample size > 250,000). We identified candidate genes with roles in cardiac energy substrate metabolism, which highlight insulin receptor signalling, in addition to the established pathways for QT and JT. Connective tissues and pathways relating to extracellular matrix interactions were significantly enriched for QRS. We also found evidence for sex-specific effects at an X-chromosome locus. Utilizing a gene-based testing approach, we identified associations with a burden of rare variants at Mendelian genes, including TNNI3K, which has not previously been reported using single-variant GWAS methods. Druggability analyses highlight new potential therapeutic targets and polygenic risk scores were associated with atrial fibrillation, conduction disease and sudden cardiac death.