1. Genetics and Genomics

Body mass index and adipose distribution have opposing genetic impacts on human blood traits

  1. Christopher S Thom  Is a corresponding author
  2. Madison B Wilken
  3. Stella T Chou
  4. Ben Voight  Is a corresponding author
  1. Children's Hospital of Philadelphia, United States
  2. University of Pennsylvania, United States
https://doi.org/10.7554/eLife.75317
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  1. Christopher S Thom
  2. Madison B Wilken
  3. Stella T Chou
  4. Ben Voight
(2022)
Body mass index and adipose distribution have opposing genetic impacts on human blood traits
eLife 11:e75317.
https://doi.org/10.7554/eLife.75317
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Abstract

Body mass index (BMI), hyperlipidemia, and truncal adipose distribution concordantly elevate cardiovascular disease risks, but have unknown genetic effects on blood trait variation. Using Mendelian randomization, we define unexpectedly opposing roles for increased BMI and truncal adipose distribution on blood traits. Elevated genetically determined BMI and lipid levels decreased hemoglobin and hematocrit levels, consistent with clinical observations associating obesity and anemia. We found that lipid-related effects were confined to erythroid traits. In contrast, BMI affected multiple blood lineages, indicating broad effects on hematopoiesis. Increased truncal adipose distribution opposed BMI effects, increasing hemoglobin and blood cell counts across lineages. Conditional analyses indicated genes, pathways, and cell types responsible for these effects, including Leptin Receptor and other blood cell-extrinsic factors in adipocytes and endothelium that regulate hematopoietic stem and progenitor cell biology. Our findings identify novel roles for obesity on hematopoiesis, including a previously underappreciated role for genetically determined adipose distribution in determining blood cell formation and function.

Data availability

The current manuscript is a computational study based on publicly available data sets, so no primary data were generated for this manuscript. All relevant coding scripts and data sets can be found on GitHub (https://github.com/thomchr/ObesityAdiposityBloodMR) or by request.

The following previously published data sets were used
    1. van der Harst and Verweij
    (2018) CAD Summary Statistics
    Mendeley Data: doi:10.17632/2zdd47c94h.1; doi:10.17632/gbbsrpx6bs.1.
    https://data.mendeley.com/datasets/2zdd47c94h/1

Article and author information

Author details

  1. Christopher S Thom

    Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, United States
    For correspondence
    thomc@chop.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1830-9922

  2. Madison B Wilken

    Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Stella T Chou

    Division of Hematology, Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Ben Voight

    Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, United States
    For correspondence
    bvoight@pennmedicine.upenn.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD043021)

  • Christopher S Thom

National Heart, Lung, and Blood Institute (K99HL156052)

  • Christopher S Thom

National Heart, Lung, and Blood Institute (U01HL124696)

  • Stella T Chou

National Institute of Diabetes and Digestive and Kidney Diseases (R01DK101478)

  • Ben Voight

National Institute of Diabetes and Digestive and Kidney Diseases (UM1DK126194)

  • Ben Voight

Linda Pechenik Montague (Investigator Award)

  • Ben Voight

Children's Hospital of Philadelphia (K-readiness award)

  • Christopher S Thom

National Heart, Lung, and Blood Institute (U24HL134763)

  • Christopher S Thom

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sara Hägg, Karolinska Institutet, Sweden

Version history

  1. Received: November 5, 2021
  2. Preprint posted: November 7, 2021 (view preprint)
  3. Accepted: February 14, 2022
  4. Accepted Manuscript published: February 15, 2022 (version 1)
  5. Version of Record published: February 28, 2022 (version 2)

Copyright

© 2022, Thom et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Christopher S Thom
  2. Madison B Wilken
  3. Stella T Chou
  4. Ben Voight
(2022)
Body mass index and adipose distribution have opposing genetic impacts on human blood traits
eLife 11:e75317.
https://doi.org/10.7554/eLife.75317

Share this article

https://doi.org/10.7554/eLife.75317

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