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Metabolome Genome-Wide Association Study Identifies 74 Novel Genomic Regions Influencing Plasma Metabolites Levels

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Pirro G. Hysi, Massimo Mangino, Paraskevi Christofidou, Mario Falchi, Edward D. Karoly, NIHR Bioresource Investigators NIHR Bioresource Investigators, Robert P. Mohney, Ana M. Valdes, Tim D. Spector, Cristina Menni

Original languageEnglish
Article number61
Pages (from-to)e61
JournalMetabolites
Volume12
Issue number1
Early online date11 Jan 2022
DOIs
Accepted/In press16 Dec 2021
E-pub ahead of print11 Jan 2022
PublishedJan 2022

Bibliographical note

Funding Information: Funding: The Department of Twin Research receives grants from the Wellcome Trust (212904/Z/18/Z) and Medical Research Council/British Heart Foundation Ancestry and Biological Informative Markers for Stratification of Hypertension (AIMHY; MR/M016560/1), and support from the European Union (H2020 grants SYSCID; 733100), the Chronic Disease Research Foundation, Zoe Global, the NIHR Clinical Research Facility and the Biomedical Research Centre (based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London). C.M. is funded by the Chronic Disease Research Foundation and by the MRC AimHy (MR/M016560/1) project grant. A.M.V. is supported by the National Institute for Health Research Nottingham Biomedical Research Centre. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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King's Authors

Abstract

Metabolites are small products of metabolism that provide a snapshot of the wellbeing of an organism and the mechanisms that control key physiological processes involved in health and disease. Here we report the results of a genome-wide association study of 722 circulating metabolite levels in 8809 subjects of European origin, providing both breadth and depth. These analyses identified 202 unique genomic regions whose variations are associated with the circulating levels of 478 different metabolites. Replication with a subset of 208 metabolites that were available in an independent dataset for a cohort of 1768 European subjects confirmed the robust associations, including 74 novel genomic regions not associated with any metabolites in previous works. This study enhances our knowledge of genetic mechanisms controlling human metabolism. Our findings have major potential for identifying novel targets and developing new therapeutic strategies.

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