Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Oct 5;91(4):721-8.
doi: 10.1016/j.ajhg.2012.08.010. Epub 2012 Sep 20.

Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population

Minoru Nakamura  1 , Nao Nishida, Minae Kawashima, Yoshihiro Aiba, Atsushi Tanaka, Michio Yasunami, Hitomi Nakamura, Atsumasai Komori, Makoto Nakamuta, Mikio Zeniya, Etsuko Hashimoto, Hiromasa Ohira, Kazuhide Yamamoto, Morikazu Onji, Shuichi Kaneko, Masao Honda, Satoshi Yamagiwa, Kazuhiko Nakao, Takafumi Ichida, Hajime Takikawa, Masataka Seike, Takeji Umemura, Yoshiyuki Ueno, Shotaro Sakisaka, Kentaro Kikuchi, Hirotoshi Ebinuma, Noriyo Yamashiki, Sumito Tamura, Yasuhiko Sugawara, Akira Mori, Shintaro Yagi, Ken Shirabe, Akinobu Taketomi, Kuniaki Arai, Kyoko Monoe, Tatsuki Ichikawa, Makiko Taniai, Yasuhiro Miyake, Teru Kumagi, Masanori Abe, Kaname Yoshizawa, Satoru Joshita, Shinji Shimoda, Koichi Honda, Hiroki Takahashi, Katsuji Hirano, Yasuaki Takeyama, Kenichi Harada, Kiyoshi Migita, Masahiro Ito, Hiroshi Yatsuhashi, Nobuyoshi Fukushima, Hajime Ota, Tatsuji Komatsu, Takeo Saoshiro, Jinya Ishida, Hirotsugu Kouno, Hirotaka Kouno, Michiyasu Yagura, Masakazu Kobayashi, Toyokichi Muro, Naohiko Masaki, Keiichi Hirata, Yukio Watanabe, Yoko Nakamura, Masaaki Shimada, Noboru Hirashima, Toshiki Komeda, Kazuhiro Sugi, Michiaki Koga, Keisuke Ario, Eiichi Takesaki, Yoshihiko Maehara, Shinji Uemoto, Norihiro Kokudo, Hirohito Tsubouchi, Masashi Mizokami, Yasuni Nakanuma, Katsushi Tokunaga, Hiromi Ishibashi
Affiliations

Genome-wide association study identifies TNFSF15 and POU2AF1 as susceptibility loci for primary biliary cirrhosis in the Japanese population

Minoru Nakamura et al. Am J Hum Genet. .

Abstract

For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

PubMed Disclaimer

Figures

Figure 1
Figure 1
GWAS Results From 963 samples (487 Japanese PBC cases and 476 Japanese healthy controls), p values were calculated with a chi-square test for allele frequencies among 420,928 SNPs.
Figure 2
Figure 2
LD Structure, p Values, and OR Plots in the Association Analysis LD maps (A) around TNFSF15 (chr9: nucleotide position: 116561403–116733452; build 36.3) and (B) around POU2AF1 (chr11: nucleotide position: 110684600–110802128; build 36.3). The middle panels show estimates of pairwise r2 for (A) 28 SNPs and (B) 33 SNPs in the high-density mapping with a total of 2,365 samples used. The bottom panels show p values and OR-based chi-square tests for the allelic model for the left panels of 963 samples in the GWAS (●), the right panels of 1,402 samples in the replication study (▴), and the combined analysis (⋄).
See this image and copyright information in PMC

References

    1. Kaplan M.M., Gershwin M.E. Primary biliary cirrhosis. N. Engl. J. Med. 2005;353:1261–1273. - PubMed
    1. Boonstra K., Beuers U., Ponsioen C.Y. Epidemiology of primary sclerosing cholangitis and primary biliary cirrhosis: a systematic review. J. Hepatol. 2012;56:1181–1188. - PubMed
    1. Selmi C., Mayo M.J., Bach N., Ishibashi H., Invernizzi P., Gish R.G., Gordon S.C., Wright H.I., Zweiban B., Podda M., Gershwin M.E. Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment. Gastroenterology. 2004;127:485–492. - PubMed
    1. Hirschfield G.M., Liu X., Xu C., Lu Y., Xie G., Lu Y., Gu X., Walker E.J., Jing K., Juran B.D. Primary biliary cirrhosis associated with HLA, IL12A, and IL12RB2 variants. N. Engl. J. Med. 2009;360:2544–2555. - PMC - PubMed
    1. Hirschfield G.M., Liu X., Han Y., Gorlov I.P., Lu Y., Xu C., Lu Y., Chen W., Juran B.D., Coltescu C. Variants at IRF5-TNPO3, 17q12-21 and MMEL1 are associated with primary biliary cirrhosis. Nat. Genet. 2010;42:655–657. - PMC - PubMed

Publication types

MeSH terms