Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS
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CitationPan, DZ. Garske, KM. Alvarez, M. Bhagat, YV. Boocock, J. Nikkola, E. Miao, Z. Raulerson, CK. Cantor, RM. Civelek, M. Glastonbury, CA. Small, KS. Boehnke, M. Lusis, AJ. Sinsheimer, JS. Mohlke, KL. Laakso, M. Pajukanta, P. Ko, A. (2018). Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS. Nature Communications, 9, 1512. 10.1038/s41467-018-03554-9.
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 obesity-related 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.
Subjectsgene expression profiling obesity
Link to the original itemhttp://dx.doi.org/10.1038/s41467-018-03554-9
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