title: Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population.
abstract: A previous genome-wide association study (GWAS) performed in 963 Japanese individuals (487 primary biliary cholangitis [PBC] cases and 476 healthy controls) identified TNFSF15 (rs4979462) and POU2AF1 (rs4938534) as strong susceptibility loci for PBC. In this study, we performed GWAS in additional 1,923 Japanese individuals (894 PBC cases and 1,029 healthy controls), and combined the results with the previous data. This GWAS, together with a subsequent replication study in an independent set of 7,024 Japanese individuals (512 PBC cases and 6,512 healthy controls), identified PRKCB (rs7404928) as a novel susceptibility locus for PBC (odds ratio [OR] = 1.26, P = 4.13 × 10-9). Furthermore, a primary functional variant of PRKCB (rs35015313) was identified by genotype imputation using a phased panel of 1,070 Japanese individuals from a prospective, general population cohort study and subsequent in vitro functional analyses. These results may lead to improved understanding of the disease pathways involved in PBC, forming a basis for prevention of PBC and development of novel therapeutics.
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Minae
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authors.lastname: Kawashima
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hitomi
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Aiba
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Division of Biomedical Information Analysis, Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
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authors.affiliation: Division of Biomedical Information Analysis, Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Yosuke
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authors.lastname: Kawai
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
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authors.affiliation: Department of Gastroenterology and Hepatology, Tokyo Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Mikio
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authors.affiliation: Department of Medicine and Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Etsuko
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authors.affiliation: Department of Gastroenterology and Rheumatic Diseases, Fukushima Medical University of Medicine, Fukushima, Japan.
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authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Matsuyama, Japan.
authors.forename: Masanori
authors.initials: M
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authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagaski, Japan.
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authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Shuichi
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authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: Masao
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authors.affiliation: Division of Gastroenterology and Hepatology, Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
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authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, Oita University, Oita, Japan.
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authors.affiliation: Department of Gastroenterology and Medicine, Fukuoka University School of Medicine, Fukuoka, Japan.
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authors.initials: O
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authors.affiliation: Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan.
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authors.initials: T
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authors.affiliation: Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagaski, Japan.
authors.forename: Hidetaka
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authors.forename: Takashi
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authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
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authors.affiliation: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
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authors.affiliation: Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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authors.affiliation: Department of Surgery and Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
authors.forename: Ken
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authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.
authors.forename: Atsumasa
authors.initials: A
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authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.
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authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.
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authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.
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authors.affiliation: Department of Clinical Medicine, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan.
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authors.affiliation: Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
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authors.forename: Yoshihiko
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authors.affiliation: Hepatobiliarypancreatic Surgery Division, Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Norihiro
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authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.
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authors.lastname: Ishibashi
authors.affiliation: Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
authors.affiliation: Division of Biomedical Information Analysis, Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Nagasaki
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Clinical Research Center, National Hospital Organization (NHO) Nagasaki Medical Center, Omura, Japan.|Headquaters of PBC Research in the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ), Clinical Research Center, NHO Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Omura, Japan.|Headquaters of gp210 Working Group in Intractable Liver Disease Research Project Team of the Ministry of Health and Welfare in Japan, Clinical Research Center, NHO Nagasaki Medical Center, Omura, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D044466:Asian People; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007564:Japan; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D064546:Protein Kinase C beta / Q000235:genetics*
chemical_list: C579054:PRKCB protein, human; D064546:Protein Kinase C beta