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 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

doi:10.1093/hmg/ddw406

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

Tohoku Medical Megabank Organization (ToMMo)

Research output: Contribution to journal › Article › peer-review

51 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 language	English
Pages (from-to)	650-659
Number of pages	10
Journal	Human Molecular Genetics
Volume	26
Issue number	3
DOIs	https://doi.org/10.1093/hmg/ddw406
Publication status	Published - 2017

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10.1093/hmg/ddw406

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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

@article{a37a19e2fd59423288f92dc468ecbb8a,

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.",

author = "Minae Kawashima and Yuki Hitomi and Yoshihiro Aiba and Nao Nishida and Kaname Kojima and Yosuke Kawai and Hitomi Nakamura and Atsushi Tanaka and Mikio Zeniya and Etsuko Hashimoto and Hiromasa Ohira and Kazuhide Yamamoto and Masanori Abe and Kazuhiko Nakao and Satoshi Yamagiwa and Shuichi Kaneko and Masao Honda and Takeji Umemura and Takafumi Ichida and Masataka Seike and Shotaro Sakisaka and Masaru Harada and Osamu Yokosuka and Yoshiyuki Ueno and Michio Senju and Tatsuo Kanda and Hidetaka Shibata and Takashi Himoto and Kazumoto Murata and Yasuhiro Miyake and Hirotoshi Ebinuma and Makiko Taniai and Satoru Joshita and Toshiki Nikami and Hajime Ota and Hiroshi Kouno and Hirotaka Kouno and Makoto Nakamuta and Nobuyoshi Fukushima and Motoyuki Kohjima and Tatsuji Komatsu and Toshiki Komeda and Yukio Ohara and Toyokichi Muro and Tsutomu Yamashita and Kaname Yoshizawa and Yoko Nakamura and Masaaki Shimada and Noboru Hirashima and Kazuhiro Sugi and Keisuke Ario and Eiichi Takesaki and Atsushi Naganuma and Hiroshi Mano and Haruhiro Yamashita and Kouki Matsushita and Kazuhiko Yamauchi and Fujio Makita and Hideo Nishimura and Kiyoshi Furuta and Naohiro Takahashi and Masahiro Kikuchi and Naohiko Masaki and Tomohiro Tanaka and Sumito Tamura and Akira Mori and Shintaro Yagi and Ken Shirabe and Atsumasa Komori and Kiyoshi Migita and Masahiro Ito and Shinya Nagaoka and Seigo Abiru and Hiroshi Yatsuhashi and Michio Yasunami and Shinji Shimoda and Kenichi Harada and Hiroto Egawa and Yoshihiko Maehara and Shinji Uemoto and Norihiro Kokudo and Hajime Takikawa and Hiromi Ishibashi and Kazuaki Chayama and Masashi Mizokami and Masao Nagasaki and Katsushi Tokunaga and Minoru Nakamura",

note = "Publisher Copyright: {\textcopyright} The Author 2016.",

year = "2017",

doi = "10.1093/hmg/ddw406",

language = "English",

volume = "26",

pages = "650--659",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "3",

}

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, Seike, M, Sakisaka, S, Harada, M, Yokosuka, O, Ueno, Y, Senju, M, Kanda, T, Shibata, H, Himoto, T, Murata, K, Miyake, Y, Ebinuma, H, Taniai, M, Joshita, S, Nikami, T, Ota, H, Kouno, H, Kouno, H, Nakamuta, M, Fukushima, N, Kohjima, M, Komatsu, T, Komeda, T, Ohara, Y, Muro, T, Yamashita, T, Yoshizawa, K, Nakamura, Y, Shimada, M, Hirashima, N, Sugi, K, Ario, K, Takesaki, E, Naganuma, A, Mano, H, Yamashita, H, Matsushita, K, Yamauchi, K, Makita, F, Nishimura, H, Furuta, K, Takahashi, N, Kikuchi, M, Masaki, N, Tanaka, T, Tamura, S, Mori, A, Yagi, S, Shirabe, K, Komori, A, Migita, K, Ito, M, Nagaoka, S, Abiru, S, Yatsuhashi, H, Yasunami, M, Shimoda, S, Harada, K, Egawa, H, Maehara, Y, Uemoto, S, Kokudo, N, Takikawa, H, Ishibashi, H, Chayama, K, Mizokami, M, Nagasaki, M, Tokunaga, K & 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, vol. 26, no. 3, pp. 650-659. https://doi.org/10.1093/hmg/ddw406

TY - JOUR

T1 - Genome-wide association studies identify PRKCB as a novel genetic susceptibility locus for primary biliary cholangitis in the Japanese population

AU - Kawashima, Minae

AU - Hitomi, Yuki

AU - Aiba, Yoshihiro

AU - Nishida, Nao

AU - Kojima, Kaname

AU - Kawai, Yosuke

AU - Nakamura, Hitomi

AU - Tanaka, Atsushi

AU - Zeniya, Mikio

AU - Hashimoto, Etsuko

AU - Ohira, Hiromasa

AU - Yamamoto, Kazuhide

AU - Abe, Masanori

AU - Nakao, Kazuhiko

AU - Yamagiwa, Satoshi

AU - Kaneko, Shuichi

AU - Honda, Masao

AU - Umemura, Takeji

AU - Ichida, Takafumi

AU - Seike, Masataka

AU - Sakisaka, Shotaro

AU - Harada, Masaru

AU - Yokosuka, Osamu

AU - Ueno, Yoshiyuki

AU - Senju, Michio

AU - Kanda, Tatsuo

AU - Shibata, Hidetaka

AU - Himoto, Takashi

AU - Murata, Kazumoto

AU - Miyake, Yasuhiro

AU - Ebinuma, Hirotoshi

AU - Taniai, Makiko

AU - Joshita, Satoru

AU - Nikami, Toshiki

AU - Ota, Hajime

AU - Kouno, Hiroshi

AU - Kouno, Hirotaka

AU - Nakamuta, Makoto

AU - Fukushima, Nobuyoshi

AU - Kohjima, Motoyuki

AU - Komatsu, Tatsuji

AU - Komeda, Toshiki

AU - Ohara, Yukio

AU - Muro, Toyokichi

AU - Yamashita, Tsutomu

AU - Yoshizawa, Kaname

AU - Nakamura, Yoko

AU - Shimada, Masaaki

AU - Hirashima, Noboru

AU - Sugi, Kazuhiro

AU - Ario, Keisuke

AU - Takesaki, Eiichi

AU - Naganuma, Atsushi

AU - Mano, Hiroshi

AU - Yamashita, Haruhiro

AU - Matsushita, Kouki

AU - Yamauchi, Kazuhiko

AU - Makita, Fujio

AU - Nishimura, Hideo

AU - Furuta, Kiyoshi

AU - Takahashi, Naohiro

AU - Kikuchi, Masahiro

AU - Masaki, Naohiko

AU - Tanaka, Tomohiro

AU - Tamura, Sumito

AU - Mori, Akira

AU - Yagi, Shintaro

AU - Shirabe, Ken

AU - Komori, Atsumasa

AU - Migita, Kiyoshi

AU - Ito, Masahiro

AU - Nagaoka, Shinya

AU - Abiru, Seigo

AU - Yatsuhashi, Hiroshi

AU - Yasunami, Michio

AU - Shimoda, Shinji

AU - Harada, Kenichi

AU - Egawa, Hiroto

AU - Maehara, Yoshihiko

AU - Uemoto, Shinji

AU - Kokudo, Norihiro

AU - Takikawa, Hajime

AU - Ishibashi, Hiromi

AU - Chayama, Kazuaki

AU - Mizokami, Masashi

AU - Nagasaki, Masao

AU - Tokunaga, Katsushi

AU - Nakamura, Minoru

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85018312958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018312958&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddw406

DO - 10.1093/hmg/ddw406

M3 - Article

C2 - 28062665

AN - SCOPUS:85018312958

SN - 0964-6906

VL - 26

SP - 650

EP - 659

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 3

ER -

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

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