2. Academic Validation
  3. Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population

Identification of critical genetic variants associated with metabolic phenotypes of the Japanese population

  • Commun Biol. 2020 Nov 11;3(1):662. doi: 10.1038/s42003-020-01383-5.
Seizo Koshiba 1 2 3,  Ikuko N Motoike 4 5,  Daisuke Saigusa 4 6,  Jin Inoue 4 6,  Yuichi Aoki 4 5,  Shu Tadaka 4 5,  Matsuyuki Shirota 4 6,  Fumiki Katsuoka 4 6 7,  Gen Tamiya 4 6 7,  Naoko Minegishi 4 6 7,  Nobuo Fuse 4 6 7,  Kengo Kinoshita 4 7 5,  Masayuki Yamamoto 8 9 10
Affiliations

Affiliations

  • 1 Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan. koshiba@megabank.tohoku.ac.jp.
  • 2 Graduate School of Medicine, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. koshiba@megabank.tohoku.ac.jp.
  • 3 The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan. koshiba@megabank.tohoku.ac.jp.
  • 4 Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
  • 5 Graduate School of Information Sciences, Tohoku University, 6-3-09, Aramaki Aza-Aoba, Aoba-ku, Sendai, 980-8579, Japan.
  • 6 Graduate School of Medicine, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
  • 7 The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
  • 8 Tohoku Medical Megabank Organization, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan. masiyamamoto@med.tohoku.ac.jp.
  • 9 Graduate School of Medicine, Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. masiyamamoto@med.tohoku.ac.jp.
  • 10 The Advanced Research Center for Innovations in Next-Generation Medicine (INGEM), Tohoku University, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan. masiyamamoto@med.tohoku.ac.jp.
PMID: 33177615 DOI: 10.1038/s42003-020-01383-5
Abstract

We performed a metabolome genome-wide association study for the Japanese population in the prospective cohort study of Tohoku Medical Megabank. By combining whole-genome Sequencing and nontarget metabolome analyses, we identified a large number of novel associations between genetic variants and plasma metabolites. Of the identified metabolite-associated genes, approximately half have already been shown to be involved in various diseases. We identified metabolite-associated genes involved in the metabolism of xenobiotics, some of which are from intestinal Microorganisms, indicating that the identified genetic variants also markedly influence the interaction between the host and symbiotic bacteria. We also identified five associations that appeared to be female-specific. A number of rare variants that influence metabolite levels were also found, and combinations of common and rare variants influenced the metabolite levels more profoundly. These results support our contention that metabolic phenotyping provides important insights into how genetic and environmental factors provoke human diseases.

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