Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population

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 SeikeShotaro 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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)650-659
Number of pages10
JournalHuman molecular genetics
Volume26
Issue number3
DOIs
Publication statusPublished - 2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Fingerprint Dive into the research topics of 'Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population'. Together they form a unique fingerprint.

  • Cite this

    Kawashima, M., Hitomi, Y., Aiba, Y., Nishida, N., Kojima, K., Kawai, Y., Nakamura, H., Tanaka, A., Zeniya, M., Hashimoto, E., Ohira, H., Yamamoto, K., Abe, M., Nakao, K., Yamagiwa, S., Kaneko, S., Honda, M., Umemura, T., Ichida, T., ... Nakamura, M. (2017). Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population. Human molecular genetics, 26(3), 650-659. https://doi.org/10.1093/hmg/ddw406