The causal variants and genes underlying thousands of cardiac genome-wide association study (GWAS) signals have yet to be identified. D’Antonio et al (Nat Commun 2023;14:1132, PMID 36854752) used spatiotemporal information on 966 RNA sequencing cardiac samples and performed an expression quantitative trait locus (eQTL) analysis to detect eQTLs considering both eGenes and eIsoforms. The authors identified 2578 eQTLs associated with a specific developmental stage, tissue, and/or cell type. Colocalization between eQTL and GWAS signals of 5 cardiac traits identified variants with high posterior probabilities for being causal in 210 GWAS loci. Pulse pressure GWAS loci are enriched for colocalization with fetal and smooth muscle eQTLs, pulse rate with adult and cardiac muscle eQTLs, and atrial fibrillation with cardiac muscle eQTLs. Fine mapping identifies 79 credible sets with ≤5 single nucleotide polymorphisms, of which 15 were associated with spatiotemporal eQTLs. The authors conclude that many cardiac GWAS variants impact traits and disease in a developmental stage-, tissue-, and/or cell type–specific fashion.
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Published online: March 07, 2023
Publication stageIn Press Journal Pre-Proof
Funding Sources: The author has no funding sources to disclose. Disclosures: The author has no conflicts of interest to disclose.
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