Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS

David Z. Pan, Kristina M. Garske, Marcus Alvarez, Yash V. Bhagat, James Boocock, Elina Nikkola, Zong Miao, Chelsea K. Raulerson, Rita M. Cantor, Mete Civelek, Craig A. Glastonbury, Kerrin S. Small, Michael Boehnke, Aldons J. Lusis, Janet S. Sinsheimer, Karen L. Mohlke, Markku Laakso, Päivi Pajukanta and Arthur Ko ()
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David Z. Pan: David Geffen School of Medicine at UCLA
Kristina M. Garske: David Geffen School of Medicine at UCLA
Marcus Alvarez: David Geffen School of Medicine at UCLA
Yash V. Bhagat: David Geffen School of Medicine at UCLA
James Boocock: David Geffen School of Medicine at UCLA
Elina Nikkola: David Geffen School of Medicine at UCLA
Zong Miao: David Geffen School of Medicine at UCLA
Chelsea K. Raulerson: University of North Carolina
Rita M. Cantor: David Geffen School of Medicine at UCLA
Mete Civelek: University of Virginia
Craig A. Glastonbury: University of Oxford
Kerrin S. Small: King’s College
Michael Boehnke: University of Michigan
Aldons J. Lusis: David Geffen School of Medicine at UCLA
Janet S. Sinsheimer: David Geffen School of Medicine at UCLA
Karen L. Mohlke: University of North Carolina
Markku Laakso: University of Eastern Finland and Kuopio University Hospital
Päivi Pajukanta: David Geffen School of Medicine at UCLA
Arthur Ko: David Geffen School of Medicine at UCLA

Nature Communications, 2018, vol. 9, issue 1, 1-11

Abstract: 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 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03554-9

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DOI: 10.1038/s41467-018-03554-9

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