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Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals

Author

Listed:
  • Usman A. Tahir

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Daniel H. Katz

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Julian Avila-Pachecho

    (Broad Institute of Harvard and MIT)

  • Alexander G. Bick

    (Broad Institute of Harvard and MIT)

  • Akhil Pampana

    (Broad Institute of Harvard and MIT)

  • Jeremy M. Robbins

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Zhi Yu

    (Broad Institute of Harvard and MIT)

  • Zsu-Zsu Chen

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Mark D. Benson

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Daniel E. Cruz

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Debby Ngo

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Shuliang Deng

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Xu Shi

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Shuning Zheng

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Aaron S. Eisman

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Laurie Farrell

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Michael E. Hall

    (University of Mississippi Medical Center)

  • Adolfo Correa

    (University of Mississippi Medical Center)

  • Russell P. Tracy

    (University of Vermont)

  • Peter Durda

    (University of Vermont)

  • Kent D. Taylor

    (The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center)

  • Yongmei Liu

    (Duke University Medical Center)

  • W. Craig Johnson

    (University of Washington)

  • Xiuqing Guo

    (The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center)

  • Jie Yao

    (The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center)

  • Yii-Der Ida Chen

    (The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center)

  • Ani W. Manichaikul

    (University of Virginia
    University of Virginia)

  • Frederick L. Ruberg

    (Boston University School of Medicine and Boston Medical Center)

  • William S. Blaner

    (Columbia University Medical Center)

  • Deepti Jain

    (University of Washington)

  • Claude Bouchard

    (Pennington Biomedical Research Center)

  • Mark A. Sarzynski

    (University of South Carolina)

  • Stephen S. Rich

    (University of Virginia
    University of Virginia)

  • Jerome I. Rotter

    (The Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center)

  • Thomas J. Wang

    (UT Southwestern Medical Center)

  • James G. Wilson

    (Beth Israel Deaconess Medical Center, Harvard Medical School)

  • Clary B. Clish

    (Broad Institute of Harvard and MIT)

  • Pradeep Natarajan

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

  • Robert E. Gerszten

    (Beth Israel Deaconess Medical Center, Harvard Medical School
    Broad Institute of Harvard and MIT)

Abstract

Integrating genetic information with metabolomics has provided new insights into genes affecting human metabolism. However, gene-metabolite integration has been primarily studied in individuals of European Ancestry, limiting the opportunity to leverage genomic diversity for discovery. In addition, these analyses have principally involved known metabolites, with the majority of the profiled peaks left unannotated. Here, we perform a whole genome association study of 2,291 metabolite peaks (known and unknown features) in 2,466 Black individuals from the Jackson Heart Study. We identify 519 locus-metabolite associations for 427 metabolite peaks and validate our findings in two multi-ethnic cohorts. A significant proportion of these associations are in ancestry specific alleles including findings in APOE, TTR and CD36. We leverage tandem mass spectrometry to annotate unknown metabolites, providing new insight into hereditary diseases including transthyretin amyloidosis and sickle cell disease. Our integrative omics approach leverages genomic diversity to provide novel insights into diverse cardiometabolic diseases.

Suggested Citation

  • Usman A. Tahir & Daniel H. Katz & Julian Avila-Pachecho & Alexander G. Bick & Akhil Pampana & Jeremy M. Robbins & Zhi Yu & Zsu-Zsu Chen & Mark D. Benson & Daniel E. Cruz & Debby Ngo & Shuliang Deng & , 2022. "Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32275-3
    DOI: 10.1038/s41467-022-32275-3
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    References listed on IDEAS

    as
    1. Rozenn N Lemaitre & Toshiko Tanaka & Weihong Tang & Ani Manichaikul & Millennia Foy & Edmond K Kabagambe & Jennifer A Nettleton & Irena B King & Lu-Chen Weng & Sayanti Bhattacharya & Stefania Bandinel, 2011. "Genetic Loci Associated with Plasma Phospholipid n-3 Fatty Acids: A Meta-Analysis of Genome-Wide Association Studies from the CHARGE Consortium," PLOS Genetics, Public Library of Science, vol. 7(7), pages 1-12, July.
    2. Robert E. Gerszten & Thomas J. Wang, 2008. "The search for new cardiovascular biomarkers," Nature, Nature, vol. 451(7181), pages 949-952, February.
    3. Karsten Suhre & So-Youn Shin & Ann-Kristin Petersen & Robert P. Mohney & David Meredith & Brigitte Wägele & Elisabeth Altmaier & Panos Deloukas & Jeanette Erdmann & Elin Grundberg & Christopher J. Ham, 2011. "Human metabolic individuality in biomedical and pharmaceutical research," Nature, Nature, vol. 477(7362), pages 54-60, September.
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