1. Whole Genome Association Study of the Plasma Metabolome Identifies Metabolites Linked to Cardiometabolic Disease in Black Individuals.
- Author
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Tahir UA, Katz DH, Avila-Pachecho J, Bick AG, Pampana A, Robbins JM, Yu Z, Chen ZZ, Benson MD, Cruz DE, Ngo D, Deng S, Shi X, Zheng S, Eisman AS, Farrell L, Hall ME, Correa A, Tracy RP, Durda P, Taylor KD, Liu Y, Johnson WC, Guo X, Yao J, Chen YI, Manichaikul AW, Ruberg FL, Blaner WS, Jain D, Bouchard C, Sarzynski MA, Rich SS, Rotter JI, Wang TJ, Wilson JG, Clish CB, Natarajan P, and Gerszten RE
- Subjects
- Black People, Humans, Metabolome genetics, Metabolomics, Tandem Mass Spectrometry, Cardiovascular Diseases ethnology, Cardiovascular Diseases genetics, Genome-Wide Association Study
- 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., (© 2022. The Author(s).)
- Published
- 2022
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