Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-02-04

AUTHORS

Ken Suzuki, Masato Akiyama, Kazuyoshi Ishigaki, Masahiro Kanai, Jun Hosoe, Nobuhiro Shojima, Atsushi Hozawa, Aya Kadota, Kiyonori Kuriki, Mariko Naito, Kozo Tanno, Yasushi Ishigaki, Makoto Hirata, Koichi Matsuda, Nakao Iwata, Masashi Ikeda, Norie Sawada, Taiki Yamaji, Motoki Iwasaki, Shiro Ikegawa, Shiro Maeda, Yoshinori Murakami, Kenji Wakai, Shoichiro Tsugane, Makoto Sasaki, Masayuki Yamamoto, Yukinori Okada, Michiaki Kubo, Yoichiro Kamatani, Momoko Horikoshi, Toshimasa Yamauchi, Takashi Kadowaki

ABSTRACT

To understand the genetics of type 2 diabetes in people of Japanese ancestry, we conducted A meta-analysis of four genome-wide association studies (GWAS; 36,614 cases and 155,150 controls of Japanese ancestry). We identified 88 type 2 diabetes–associated loci (P < 5.0 × 10−8) with 115 independent signals (P < 5.0 × 10−6), of which 28 loci with 30 signals were novel. Twenty-eight missense variants were in linkage disequilibrium (r2 > 0.6) with the lead variants. Among the 28 missense variants, three previously unreported variants had distinct minor allele frequency (MAF) spectra between people of Japanese and European ancestry (MAFJPN > 0.05 versus MAFEUR < 0.01), including missense variants in genes related to pancreatic acinar cells (GP2) and insulin secretion (GLP1R). Transethnic comparisons of the molecular pathways identified from the GWAS results highlight both ethnically shared and heterogeneous effects of a series of pathways on type 2 diabetes (for example, monogenic diabetes and beta cells). More... »

PAGES

379-386

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    3

    VOLUME

    51

    Author Affiliations

  • Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
  • Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • Graduate School of Medicine, Tohoku University, Sendai, Japan
  • Department of Public Health, Shiga University of Medical Science, Otsu, Japan
  • Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
  • Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
  • Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, Japan
  • Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
  • Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
  • Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
  • Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
  • Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
  • Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Nishihara, Japan
  • Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
  • Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
  • Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
  • Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan
  • Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan
  • RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Kyoto-McGill International Collaborative School in Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
  • Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
  • Department of Metabolism and Nutrition, Mizonokuchi Hospital, Faculty of Medicine, Teikyo University, Tokyo, Japan
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0332-4

    DOI

    http://dx.doi.org/10.1038/s41588-018-0332-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1111916178

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30718926


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