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Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots

Author

Listed:
  • Saaket Agrawal

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Minxian Wang

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Beijing Institute of Genomics, Chinese Academy of Sciences)

  • Marcus D. R. Klarqvist

    (Broad Institute of MIT and Harvard)

  • Kirk Smith

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Joseph Shin

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Hesam Dashti

    (Broad Institute of MIT and Harvard)

  • Nathaniel Diamant

    (Broad Institute of MIT and Harvard)

  • Seung Hoan Choi

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital)

  • Sean J. Jurgens

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Amsterdam UMC, University of Amsterdam)

  • Patrick T. Ellinor

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Anthony Philippakis

    (Broad Institute of MIT and Harvard
    Broad Institute of MIT and Harvard)

  • Melina Claussnitzer

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Kenney Ng

    (Center for Computational Health, IBM Research)

  • Miriam S. Udler

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School)

  • Puneet Batra

    (Broad Institute of MIT and Harvard)

  • Amit V. Khera

    (Broad Institute of MIT and Harvard
    Massachusetts General Hospital
    Harvard Medical School
    Verve Therapeutics)

Abstract

For any given level of overall adiposity, individuals vary considerably in fat distribution. The inherited basis of fat distribution in the general population is not fully understood. Here, we study up to 38,965 UK Biobank participants with MRI-derived visceral (VAT), abdominal subcutaneous (ASAT), and gluteofemoral (GFAT) adipose tissue volumes. Because these fat depot volumes are highly correlated with BMI, we additionally study six local adiposity traits: VAT adjusted for BMI and height (VATadj), ASATadj, GFATadj, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 250 independent common variants (39 newly-identified) associated with at least one trait, with many associations more pronounced in female participants. Rare variant association studies extend prior evidence for PDE3B as an important modulator of fat distribution. Local adiposity traits (1) highlight depot-specific genetic architecture and (2) enable construction of depot-specific polygenic scores that have divergent associations with type 2 diabetes and coronary artery disease. These results – using MRI-derived, BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.

Suggested Citation

  • Saaket Agrawal & Minxian Wang & Marcus D. R. Klarqvist & Kirk Smith & Joseph Shin & Hesam Dashti & Nathaniel Diamant & Seung Hoan Choi & Sean J. Jurgens & Patrick T. Ellinor & Anthony Philippakis & Me, 2022. "Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30931-2
    DOI: 10.1038/s41467-022-30931-2
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    1. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Saaket Agrawal & Marcus D. R. Klarqvist & Nathaniel Diamant & Takara L. Stanley & Patrick T. Ellinor & Nehal N. Mehta & Anthony Philippakis & Kenney Ng & Melina Claussnitzer & Steven K. Grinspoon & Pu, 2023. "BMI-adjusted adipose tissue volumes exhibit depot-specific and divergent associations with cardiometabolic diseases," Nature Communications, Nature, vol. 14(1), pages 1-10, December.

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