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- Title
Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS.
- Authors
Pan, David Z.; Garske, Kristina M.; Alvarez, Marcus; Bhagat, Yash V.; Boocock, James; Nikkola, Elina; Zong Miao; Raulerson, Chelsea K.; Cantor, Rita M.; Civelek, Mete; Glastonbury, Craig A.; Small, Kerrin S.; Boehnke, Michael; Lusis, Aldons J.; Sinsheimer, Janet S.; Mohlke, Karen L.; Laakso, Markku; Pajukanta, Päivi; Ko, Arthur
- Abstract
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesityrelated phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression. We further intersect these data with published genome-wide association studies for BMI and BMI-related metabolic traits to identify the genes that are under genetic cis regulation in human adipocytes via chromosomal interactions. This integrative genomics approach identifies four cis-eQTL-eGene relationships associated with BMI or obesity-related traits, including rs4776984 and MAP2K5, which we further confirm by EMSA, and highlights 38 additional candidate genes.
- Subjects
FAT cells; GENE expression; OBESITY; PHENOTYPES; TRANSCRIPTION factors; HERITABILITY
- Publication
Nature Communications, 2018, Vol 9, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-03554-9