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

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, Xu Shi, Shuning Zheng, Aaron S. Eisman, Laurie Farrell, Michael E. Hall, Adolfo Correa, Russell P. Tracy, Peter Durda, Kent D. Taylor, Yongmei Liu, W. Craig Johnson, Xiuqing Guo, Jie Yao, Yii- Der Ida Chen, Ani W. Manichaikul, Frederick L. Ruberg, William S. Blaner, Deepti Jain, Claude Bouchard, Mark A. Sarzynski, Stephen S. Rich, Jerome I. Rotter, Thomas J. Wang, James G. Wilson, Clary B. Clish, Pradeep Natarajan and Robert E. Gerszten ()
Additional contact information
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
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
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
Robert E. Gerszten: Beth Israel Deaconess Medical Center, Harvard Medical School

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-32275-3

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