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         headline:Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population
         description: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). Genome-wide association analyses identify 28 new susceptibility loci for type 2 diabetes in the Japanese population. Transethnic comparisons highlight the key role of beta cell dysfunction in type 2 diabetes across different ancestry groups.
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      headline:Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population
      description: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). Genome-wide association analyses identify 28 new susceptibility loci for type 2 diabetes in the Japanese population. Transethnic comparisons highlight the key role of beta cell dysfunction in type 2 diabetes across different ancestry groups.
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         Type 2 diabetes
         Biomedicine
         general
         Human Genetics
         Cancer Research
         Agriculture
         Gene Function
         Animal Genetics and Genomics
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               name:Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
               type:PostalAddress
            type:Organization
      name:Mariko Naito
      affiliation:
            name:Nagoya University Graduate School of Medicine
            address:
               name:Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
               type:PostalAddress
            type:Organization
            name:Hiroshima University
            address:
               name:Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
               type:PostalAddress
            type:Organization
      name:Kozo Tanno
      affiliation:
            name:Iwate Medical University
            address:
               name:Division of Clinical Research and Epidemiology, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Iwate, Japan
               type:PostalAddress
            type:Organization
            name:Iwate Medical University
            address:
               name:Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, Japan
               type:PostalAddress
            type:Organization
      name:Yasushi Ishigaki
      affiliation:
            name:Iwate Medical University
            address:
               name:Division of Innovation & Education, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Iwate, Japan
               type:PostalAddress
            type:Organization
            name:Iwate Medical University
            address:
               name:Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
               type:PostalAddress
            type:Organization
      name:Makoto Hirata
      url:http://orcid.org/0000-0002-9994-9958
      affiliation:
            name:Institute of Medical Science, The University of Tokyo
            address:
               name:Institute of Medical Science, The University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Koichi Matsuda
      url:http://orcid.org/0000-0001-7292-2686
      affiliation:
            name:The University of Tokyo
            address:
               name:Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Nakao Iwata
      url:http://orcid.org/0000-0003-3189-6076
      affiliation:
            name:Fujita Health University School of Medicine
            address:
               name:Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
               type:PostalAddress
            type:Organization
      name:Masashi Ikeda
      affiliation:
            name:Fujita Health University School of Medicine
            address:
               name:Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
               type:PostalAddress
            type:Organization
      name:Norie Sawada
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            name:National Cancer Center
            address:
               name:Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Taiki Yamaji
      affiliation:
            name:National Cancer Center
            address:
               name:Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Motoki Iwasaki
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            name:National Cancer Center
            address:
               name:Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
               type:PostalAddress
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      name:Shiro Ikegawa
      affiliation:
            name:RIKEN Center for Integrative Medical Sciences
            address:
               name:Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Shiro Maeda
      affiliation:
            name:RIKEN Centre for Integrative Medical Sciences
            address:
               name:Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name:Graduate School of Medicine, University of the Ryukyus
            address:
               name:Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
               type:PostalAddress
            type:Organization
            name:University of the Ryukyus Hospital
            address:
               name:Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Nishihara, Japan
               type:PostalAddress
            type:Organization
      name:Yoshinori Murakami
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            name:Institute of Medical Science, The University of Tokyo
            address:
               name:Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Kenji Wakai
      affiliation:
            name:Nagoya University Graduate School of Medicine
            address:
               name:Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
               type:PostalAddress
            type:Organization
      name:Shoichiro Tsugane
      url:http://orcid.org/0000-0003-4105-2774
      affiliation:
            name:National Cancer Center
            address:
               name:Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
               type:PostalAddress
            type:Organization
      name:Makoto Sasaki
      url:http://orcid.org/0000-0002-3108-4361
      affiliation:
            name:Iwate Medical University
            address:
               name:Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Iwate, Japan
               type:PostalAddress
            type:Organization
            name:Iwate Medical University
            address:
               name:Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan
               type:PostalAddress
            type:Organization
      name:Masayuki Yamamoto
      affiliation:
            name:Tohoku University
            address:
               name:Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
               type:PostalAddress
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            name:Graduate School of Medicine, Tohoku University
            address:
               name:Graduate School of Medicine, Tohoku University, Sendai, Japan
               type:PostalAddress
            type:Organization
      name:Yukinori Okada
      url:http://orcid.org/0000-0002-0311-8472
      affiliation:
            name:RIKEN Center for Integrative Medical Sciences
            address:
               name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name:Osaka University Graduate School of Medicine
            address:
               name:Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
               type:PostalAddress
            type:Organization
            name:Osaka University
            address:
               name:Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan
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            name:RIKEN Center for Integrative Medical Sciences
            address:
               name:RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
               type:PostalAddress
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      name:Yoichiro Kamatani
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      affiliation:
            name:RIKEN Center for Integrative Medical Sciences
            address:
               name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name:Kyoto University Graduate School of Medicine
            address:
               name:Kyoto-McGill International Collaborative School in Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Momoko Horikoshi
      affiliation:
            name:RIKEN Centre for Integrative Medical Sciences
            address:
               name:Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Toshimasa Yamauchi
      url:http://orcid.org/0000-0003-4827-6404
      affiliation:
            name:The University of Tokyo
            address:
               name:Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Takashi Kadowaki
      url:http://orcid.org/0000-0002-5428-3582
      affiliation:
            name:The University of Tokyo
            address:
               name:Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
            name:The University of Tokyo
            address:
               name:Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
               type:PostalAddress
            type:Organization
            name:Teikyo University
            address:
               name:Department of Metabolism and Nutrition, Mizonokuchi Hospital, Faculty of Medicine, Teikyo University, Tokyo, Japan
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
      name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
      name:Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
      name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
      name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Department of Biomedical Informatics, Harvard Medical School, Boston, USA
      name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
      name:Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
      name:Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
      name:Graduate School of Medicine, Tohoku University, Sendai, Japan
      name:Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan
      name:Department of Public Health, Shiga University of Medical Science, Otsu, Japan
      name:Laboratory of Public Health, School of Food and Nutritional Sciences, University of Shizuoka, Shizuoka, Japan
      name:Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
      name:Department of Oral Epidemiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
      name:Division of Clinical Research and Epidemiology, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Iwate, Japan
      name:Department of Hygiene and Preventive Medicine, School of Medicine, Iwate Medical University, Iwate, Japan
      name:Division of Innovation & Education, Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Iwate, Japan
      name:Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan
      name:Institute of Medical Science, The University of Tokyo, Tokyo, Japan
      name:Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan
      name:Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
      name:Department of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan
      name:Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
      name:Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
      name:Division of Epidemiology, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
      name:Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo, Japan
      name:Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
      name:Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan
      name:Division of Clinical Laboratory and Blood Transfusion, University of the Ryukyus Hospital, Nishihara, Japan
      name:Division of Molecular Pathology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan
      name:Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan
      name:Center for Public Health Sciences, National Cancer Center, Tokyo, Japan
      name:Iwate Tohoku Medical Megabank Organization, Disaster Reconstruction Center, Iwate Medical University, Iwate, Japan
      name:Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Iwate, Japan
      name:Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan
      name:Graduate School of Medicine, Tohoku University, Sendai, Japan
      name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan
      name:Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan
      name:RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
      name:Kyoto-McGill International Collaborative School in Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
      name:Laboratory for Endocrinology, Metabolism and Kidney Diseases, RIKEN Centre for Integrative Medical Sciences, Yokohama, Japan
      name:Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
      name:Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
      name:Department of Prevention of Diabetes and Lifestyle-Related Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
      name:Department of Metabolism and Nutrition, Mizonokuchi Hospital, Faculty of Medicine, Teikyo University, Tokyo, Japan
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