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

Author

Listed:
  • David Z. Pan

    (David Geffen School of Medicine at UCLA
    Bioinformatics Interdepartmental Program, 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
    Bioinformatics Interdepartmental Program, 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
    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
    Bioinformatics Interdepartmental Program, UCLA
    Molecular Biology Institute at UCLA)

  • Arthur Ko

    (David Geffen School of Medicine at UCLA
    Molecular Biology Institute at UCLA)

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.

Suggested Citation

  • 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, 2018. "Integration of human adipocyte chromosomal interactions with adipose gene expression prioritizes obesity-related genes from GWAS," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03554-9
    DOI: 10.1038/s41467-018-03554-9
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    Cited by:

    1. Long Jin & Danyang Wang & Jiaman Zhang & Pengliang Liu & Yujie Wang & Yu Lin & Can Liu & Ziyin Han & Keren Long & Diyan Li & Yu Jiang & Guisen Li & Yu Zhang & Jingyi Bai & Xiaokai Li & Jing Li & Lu Lu, 2023. "Dynamic chromatin architecture of the porcine adipose tissues with weight gain and loss," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Liam McAllan & Damir Baranasic & Sergio Villicaña & Scarlett Brown & Weihua Zhang & Benjamin Lehne & Marco Adamo & Andrew Jenkinson & Mohamed Elkalaawy & Borzoueh Mohammadi & Majid Hashemi & Nadia Fer, 2023. "Integrative genomic analyses in adipocytes implicate DNA methylation in human obesity and diabetes," Nature Communications, Nature, vol. 14(1), pages 1-20, December.

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