A Promoter Interaction Map for Cardiovascular Disease Genetics
eLIFE. 2018-07-10;
- Abstract
- Over 500 genetic loci have been associated with risk of cardiovascular diseases (CVDs); however, most loci are located in gene-distal non-coding regions and their target genes are not known. Here, we generated high-resolution promoter capture Hi-C (PCHi-C) maps in human induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes (CMs) to provide a resource for identifying and prioritizing the functional targets of CVD associations. We validate these maps by demonstrating that promoters preferentially contact distal sequences enriched for tissue-specific transcription factor motifs and are enriched for chromatin marks that correlate with dynamic changes in gene expression. Using the CM PCHi-C map, we linked 1999 CVD-associated SNPs to 347 target genes. Remarkably, more than 90% of SNP-target gene interactions did not involve the nearest gene, while 40% of SNPs interacted with at least two genes, demonstrating the importance of considering long-range chromatin interactions when interpreting functional targets of disease loci.
- Consortium data used in this publication
- E-MTAB-6014 and E-MTAB-6013
- Datasets
- DSR535XNG, DSR722REK, DSR382TEU, DSR763JZB, DSR835LRF, DSR748GIJ, DSR259JVL, DSR991ZOB, DSR854NSN, DSR804DQM, DSR360EAO
- References