Genetic influences on human blood metabolites in the Japanese population

Takeshi Iwasaki; Yoichiro Kamatani; Kazuhiro Sonomura; Shuji Kawaguchi; Takahisa Kawaguchi; Meiko Takahashi; Koichiro Ohmura; Taka-Aki Sato; Fumihiko Matsuda

doi:10.1016/j.isci.2022.105738

Genetic influences on human blood metabolites in the Japanese population

iScience. 2022 Dec 6;26(1):105738. doi: 10.1016/j.isci.2022.105738. eCollection 2023 Jan 20.

Authors

Affiliations

¹ Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
² Department of Rheumatology and Clinical Immunology, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
³ Life Science Research Center, Shimadzu Corporation, Kyoto 604-8511, Japan.

Abstract

An increase in ethnic diversity in genetic studies has the potential to provide unprecedented insights into how genetic variations influence human phenotypes. In this study, we conducted a quantitative trait locus (QTL) analysis of 121 metabolites measured using gas chromatography-mass spectrometry with plasma samples from 4,888 Japanese individuals. We found 60 metabolite-gene associations, of which 13 have not been previously reported. Meta-analyses with another Japanese and a European study identified six and two additional unreported loci, respectively. Genetic variants influencing metabolite levels were more enriched in protein-coding regions than in the regulatory regions while being associated with the risk of various diseases. Finally, we identified a signature of strong negative selection for uric acid ( $\hat{S}$ = -1.53, p = 6.2 × 10^-18). Our study expanded the knowledge of genetic influences on human blood metabolites, providing valuable insights into their physiological, pathological, and selective properties.

Keywords: Human Genetics; Human Physiology; Human metabolism.

Abstract

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