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Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations

Author

Listed:
  • Elena V. Feofanova

    (The University of Texas Health Science Center)

  • Michael R. Brown

    (The University of Texas Health Science Center)

  • Taryn Alkis

    (The University of Texas Health Science Center)

  • Astrid M. Manuel

    (The University of Texas Health Science Center at Houston)

  • Xihao Li

    (Harvard T.H. Chan School of Public Health)

  • Usman A. Tahir

    (Harvard Medical School)

  • Zilin Li

    (Harvard T.H. Chan School of Public Health
    Indiana University School of Medicine)

  • Kevin M. Mendez

    (Brigham and Women’s Hospital and Harvard Medical School
    Harvard Medical School)

  • Rachel S. Kelly

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Qibin Qi

    (Albert Einstein College of Medicine)

  • Han Chen

    (The University of Texas Health Science Center
    The University of Texas Health Science Center at Houston)

  • Martin G. Larson

    (Boston University School of Public Health)

  • Rozenn N. Lemaitre

    (University of Washington)

  • Alanna C. Morrison

    (The University of Texas Health Science Center)

  • Charles Grieser

    (Metabolon Inc.)

  • Kari E. Wong

    (Metabolon Inc.)

  • Robert E. Gerszten

    (Fred Hutchinson Cancer Research Center
    Broad Institute of Harvard and MIT)

  • Zhongming Zhao

    (The University of Texas Health Science Center
    The University of Texas Health Science Center at Houston)

  • Jessica Lasky-Su

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Bing Yu

    (The University of Texas Health Science Center)

Abstract

Circulating metabolite levels may reflect the state of the human organism in health and disease, however, the genetic architecture of metabolites is not fully understood. We have performed a whole-genome sequencing association analysis of both common and rare variants in up to 11,840 multi-ethnic participants from five studies with up to 1666 circulating metabolites. We have discovered 1985 novel variant-metabolite associations, and validated 761 locus-metabolite associations reported previously. Seventy-nine novel variant-metabolite associations have been replicated, including three genetic loci located on the X chromosome that have demonstrated its involvement in metabolic regulation. Gene-based analysis have provided further support for seven metabolite-replicated loci pairs and their biologically plausible genes. Among those novel replicated variant-metabolite pairs, follow-up analyses have revealed that 26 metabolites have colocalized with 21 tissues, seven metabolite-disease outcome associations have been putatively causal, and 7 metabolites might be regulated by plasma protein levels. Our results have depicted the genetic contribution to circulating metabolite levels, providing additional insights into understanding human disease.

Suggested Citation

  • Elena V. Feofanova & Michael R. Brown & Taryn Alkis & Astrid M. Manuel & Xihao Li & Usman A. Tahir & Zilin Li & Kevin M. Mendez & Rachel S. Kelly & Qibin Qi & Han Chen & Martin G. Larson & Rozenn N. L, 2023. "Whole-Genome Sequencing Analysis of Human Metabolome in Multi-Ethnic Populations," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38800-2
    DOI: 10.1038/s41467-023-38800-2
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    References listed on IDEAS

    as
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