Genetic influences on human blood metabolites in the Japanese population

An increase in ethnic diversity in genetic studies has the potential to provide un-precedented 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 nega-tive selection for uric acid ((S) over cap=-1.53, p = 6.2 3 10(-18)). Our study expanded the knowledge of genetic influences on human blood metabolites, providing valuable insights into their physiological, pathological, and selective properties.

Automated summary

An increase in ethnic diversity in genetic studies has allowed researchers to uncover new associations between genetic variations and human phenotypes. In this study, metabolite-gene associations were analyzed in 4,888 Japanese individuals, leading to the discovery of 60 associations, with 13 previously unreported. Meta-analyses with other Japanese and European studies revealed additional unreported loci. The study also found that genetic variants influencing metabolite levels were enriched in protein-coding regions and associated with disease risks. Furthermore, a strong negative selection signature for uric acid was identified. These findings expand our understanding of genetic influences on blood metabolites and provide insights into their physiological, pathological, and selective properties.