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

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 multiple C2 and trans-membrane domain containing two (MCTP2) and nuclear receptor subfamily two group F member two (NR2F2), both of which are known causative genes for congenital heart disease.

These candidate variants are potential risk factors for heart failure in the Japanese population.