Genome-wide association studies identifyPRKCBas a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population
Year: 2016
Type: article
Study design: Observational Study
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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddw406
Authors: Minae Kawashima, Yuki Hitomi, Yoshihiro Aiba, Nao Nishida, Kaname Kojima, Yosuke Kawai, Hitomi Nakamura, Atsushi Tanaka, Mikio Zeniya, Etsuko Hashimoto, Hiromasa Ohira, Kazuhide Yamamoto, Masanori Abe, Kazuhiko Nakao, Satoshi Yamagiwa, Shuichi Kaneko, Masao Honda, Takeji Umemura, Takafumi Ichida, Masataka Seike, Shotaro Sakisaka, Masaru Harada, Osamu Yokosuka, Yoshiyuki Ueno, Michio Senju, Tatsuo Kanda, Hidetaka Shibata, Takashi Himoto, Kazumoto Murata, Yasuhiro Miyake, Hirotoshi Ebinuma, Makiko Taniai, Satoru Joshita, Toshiki Nikami, Hajime Ota, Hiroshi Kouno, Hirotaka Kouno, Makoto Nakamuta, Nobuyoshi Fukushima, Motoyuki Kohjima, Tatsuji Komatsu, Toshiki Komeda, Yukio Ohara, Toyokichi Muro, Tsutomu Yamashita, Kaname Yoshizawa, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Kazuhiro Sugi, Keisuke Ario, Eiichi Takesaki, Atsushi Naganuma, Hiroshi Mano, Haruhiro Yamashita, Kouki Matsushita, Kazuhiko Yamauchi, Fujio Makita, Hideo Nishimura, Kiyoshi Furuta, Naohiro Takahashi, Masahiro Kikuchi, Naohiko Masaki, Tomohiro Tanaka, Sumito Tamura, Akira Mori, Shintaro Yagi, Ken Shirabe, Atsumasa Komori, Kiyoshi Migita, Masahiro Ito, Shinya Nagaoka, Seigo Abiru, Hiroshi Yatsuhashi, Michio Yasunami, Shinji Shimoda, Kenichi Harada, Hiroto Egawa, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Hajime Takikawa, Hiromi Ishibashi, Kazuaki Chayama, Masashi Mizokami, Masao Nagasaki, Katsushi Tokunaga, Minoru Nakamura
Institutions: The University of Tokyo, Nagasaki Medical Center, National Hospital Organization, National Center for Global Health and Medicine, Tohoku University, Tohoku Medical Megabank Organization, Teikyo University, Jikei University School of Medicine, Tokyo Women's Medical University, Fukushima Medical University, Okayama University, Ehime University, Nagasaki University, Niigata University, Kanazawa University, Shinshu University, Shinshu University Hospital, Juntendo University, Juntendo University Shizuoka Hospital, Oita University, Fukuoka University, University of Occupational and Environmental Health Japan, Chiba University, Yamagata University, Yamagata University Hospital, Kagawa Prefectural College of Health Sciences, Keio University, Kyoto University, Kyushu University, Institute of Tropical Medicine, Nagasaki University, Institute of Gastroenterology, Tokyo Women's Medical University, Hiroshima University
Language: English
Topic: Liver Diseases and Immunity
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Awards: Clarification of the molecular mechanisms of pathogenesis caused by PBC susceptibility polymorphisms, Whole-exome sequencing identifies a novel genetic susceptibility locus in autoimmune liver diseases, G2226317539, G2617228829, IL33/ST2 pathway involvement in the pathogenesis and disease progression of primary biliary cholangitis, G3608009314, Pyrosequencing using liver biopsy specimens for evaluating pathogenesis of cholestatic liver diseases., Analysis of molecular mechanisms involved in progression to jaundice and liver failure in primary biliary cholangitis, G4897621117, G6849506502, Searching for the genetic factors predisposing to PBC, Analysis of disease-pathways and molecular targets by disease-susceptibility genes in primary biliary cholangitis, Identification of biomarkers to predict HCC development after successful treatment of viral hepatitis, Genome-wide associationstudy to detect disease-associated genes in Japanese patients with primary biliary cirrhosis
OpenAlex ID: W2571345089