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

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Aug 22

PMID 35995766

Authors

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

Robert E Gerszten

Affiliations

Soon will be listed here.

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.

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