TY - JOUR TI - A promoter interaction map for cardiovascular disease genetics AU - Montefiori, Lindsey E AU - Sobreira, Debora R AU - Sakabe, Noboru J AU - Aneas, Ivy AU - Joslin, Amelia C AU - Hansen, Grace T AU - Bozek, Grazyna AU - Moskowitz, Ivan P AU - McNally, Elizabeth M AU - Nóbrega, Marcelo A A2 - Dekker, Job A2 - McCarthy, Mark I VL - 7 PY - 2018 DA - 2018/07/10 SP - e35788 C1 - eLife 2018;7:e35788 DO - 10.7554/eLife.35788 UR - https://doi.org/10.7554/eLife.35788 AB - 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. KW - capture Hi-C KW - cardiomyocytes KW - GWAS KW - gene regulation KW - cardiovascular disease JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -