A promoter interaction map for cardiovascular disease genetics

Lindsey E. Montefiori, Debora R. Sobreira, Noboru J. Sakabe, Ivy Aneas, Amelia C. Joslin, Grace T. Hansen, Grazyna Bozek, Ivan P. Moskowitz, Elizabeth M. McNally, Marcelo A. Nóbrega*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


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.

Original languageEnglish (US)
Article numbere35788
StatePublished - Jul 10 2018

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)


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