Identifying novel Japanese heart failure variants via endothelial cis-regulatory element analysis

Abstract

The detailed molecular mechanisms and disease risk factors for heart failure, especially in the Japanese population, remain to be identified. In this study, we developed a trans-omics approach integrating multi-omics data to explore potential disease risk factors on a genome-wide scale. We functionally annotated the single-nucleotide polymorphisms (SNPs) investigated in a Japanese heart failure genome-wide association study using the epigenome data of cis-regulatory elements and regulome data of the transcription factor-binding regions identified in vascular endothelial cells. rs3176334, located in the promoter region of CDKN1A, and rs12437763, located in an enhancer, were identified as candidate heart failure-associated SNPs in the Japanese population. Furthermore, the downstream genes regulated by the enhancer containing rs12437763 were predicted to be MCTP2 and NR2F2, both of which are known causative genes for congenital heart disease. Thus, these candidate variants are potential risk factors for heart failure in the Japanese population.