Abstract
The causal variants and genes underlying thousands of cardiac GWAS signals have yet to be identified. To address this issue, we leveraged spatiotemporal information on 966 RNA-seq cardiac samples and performed an expression quantitative trait locus (eQTL) analysis detecting ~26,000 eQTL signals associated with more than 11,000 eGenes and 7,000 eIsoforms. Approximately 2,500 eQTLs were associated with specific cardiac stages, organs, tissues and/or cell types. Colocalization and fine mapping of eQTL and GWAS signals of five cardiac traits in the UK BioBank identified variants with high posterior probabilities for being causal in 210 GWAS loci. Over 50 of these loci represent novel functionally annotated cardiac GWAS signals. Our study provides a comprehensive resource mapping regulatory variants that function in spatiotemporal context-specific manners to regulate cardiac gene expression, which can be used to functionally annotate genomic loci associated with cardiac traits and disease.
Competing Interest Statement
The authors have declared no competing interest.