Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population

Yoshihiro Aiba, Keiko Yamazaki, Nao Nishida, Minae Kawashima, Yuki Hitomi, Hitomi Nakamura, Atsumasa Komori, Yuta Fuyuno, Atsushi Takahashi, Takaaki Kawaguchi, Masakazu Takazoe, Yasuo Suzuki, Satoshi Motoya, Toshiyuki Matsui, Motohiro Esaki, Takayuki Matsumoto, Michiaki Kubo, Katsushi Tokunaga, Minoru Nakamura

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Abstract

We previously identified TNFSF15 as the most significant susceptibility gene at non-HLA loci for both primary biliary cirrhosis (PBC) and Crohn's diseases (CD) in the Japanese population. The aim of this study is to identify further disease susceptibility genes shared by PBC and CD. We selected 15 and 33 genetic variants that were significantly associated with PBC and CD, respectively, based on previously reported genome-wide association studies of the Japanese population. Next, an association study was independently performed for these genetic variants in CD (1312 CD patients and 3331 healthy controls) and PBC (1279 PBC patients and 1015 healthy controls) cohorts. Two CD susceptibility genes, ICOSLG rs2838519 and IL12B rs6556412, were also nominally associated with susceptibility to PBC (P=3.85 × 10 -2 and P=8.40 × 10 -3, respectively). Three PBC susceptibility genes, CXCR5 rs6421571, STAT4 rs7574865 and NFKB1 rs230534, were nominally associated with susceptibility to CD (P=2.82 × 10 -2, P=3.88 × 10 -2 and P=2.04 × 10 -2, respectively). The effect of ICOSLG and CXCR5 variants were concordant but the effect of STAT4, NFKB1 and IL12B variants were discordant for PBC and CD. TNFSF15 and ICOSLG-CXCR5 might constitute a shared pathogenic pathway in the development of PBC and CD in the Japanese population, whereas IL12B-STAT4-NFKB1 might constitute an opposite pathogenic pathway, reflecting the different balance between Th1 and Th17 in the two diseases.

Original languageEnglish
Pages (from-to)525-531
Number of pages7
JournalJournal of Human Genetics
Volume60
Issue number9
DOIs
Publication statusPublished - 29-09-2015

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Biliary Liver Cirrhosis
Disease Susceptibility
Crohn Disease
Population
Genes
Genome-Wide Association Study

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Aiba, Y., Yamazaki, K., Nishida, N., Kawashima, M., Hitomi, Y., Nakamura, H., ... Nakamura, M. (2015). Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population. Journal of Human Genetics, 60(9), 525-531. https://doi.org/10.1038/jhg.2015.59
Aiba, Yoshihiro ; Yamazaki, Keiko ; Nishida, Nao ; Kawashima, Minae ; Hitomi, Yuki ; Nakamura, Hitomi ; Komori, Atsumasa ; Fuyuno, Yuta ; Takahashi, Atsushi ; Kawaguchi, Takaaki ; Takazoe, Masakazu ; Suzuki, Yasuo ; Motoya, Satoshi ; Matsui, Toshiyuki ; Esaki, Motohiro ; Matsumoto, Takayuki ; Kubo, Michiaki ; Tokunaga, Katsushi ; Nakamura, Minoru. / Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population. In: Journal of Human Genetics. 2015 ; Vol. 60, No. 9. pp. 525-531.
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abstract = "We previously identified TNFSF15 as the most significant susceptibility gene at non-HLA loci for both primary biliary cirrhosis (PBC) and Crohn's diseases (CD) in the Japanese population. The aim of this study is to identify further disease susceptibility genes shared by PBC and CD. We selected 15 and 33 genetic variants that were significantly associated with PBC and CD, respectively, based on previously reported genome-wide association studies of the Japanese population. Next, an association study was independently performed for these genetic variants in CD (1312 CD patients and 3331 healthy controls) and PBC (1279 PBC patients and 1015 healthy controls) cohorts. Two CD susceptibility genes, ICOSLG rs2838519 and IL12B rs6556412, were also nominally associated with susceptibility to PBC (P=3.85 × 10 -2 and P=8.40 × 10 -3, respectively). Three PBC susceptibility genes, CXCR5 rs6421571, STAT4 rs7574865 and NFKB1 rs230534, were nominally associated with susceptibility to CD (P=2.82 × 10 -2, P=3.88 × 10 -2 and P=2.04 × 10 -2, respectively). The effect of ICOSLG and CXCR5 variants were concordant but the effect of STAT4, NFKB1 and IL12B variants were discordant for PBC and CD. TNFSF15 and ICOSLG-CXCR5 might constitute a shared pathogenic pathway in the development of PBC and CD in the Japanese population, whereas IL12B-STAT4-NFKB1 might constitute an opposite pathogenic pathway, reflecting the different balance between Th1 and Th17 in the two diseases.",
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Aiba, Y, Yamazaki, K, Nishida, N, Kawashima, M, Hitomi, Y, Nakamura, H, Komori, A, Fuyuno, Y, Takahashi, A, Kawaguchi, T, Takazoe, M, Suzuki, Y, Motoya, S, Matsui, T, Esaki, M, Matsumoto, T, Kubo, M, Tokunaga, K & Nakamura, M 2015, 'Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population', Journal of Human Genetics, vol. 60, no. 9, pp. 525-531. https://doi.org/10.1038/jhg.2015.59

Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population. / Aiba, Yoshihiro; Yamazaki, Keiko; Nishida, Nao; Kawashima, Minae; Hitomi, Yuki; Nakamura, Hitomi; Komori, Atsumasa; Fuyuno, Yuta; Takahashi, Atsushi; Kawaguchi, Takaaki; Takazoe, Masakazu; Suzuki, Yasuo; Motoya, Satoshi; Matsui, Toshiyuki; Esaki, Motohiro; Matsumoto, Takayuki; Kubo, Michiaki; Tokunaga, Katsushi; Nakamura, Minoru.

In: Journal of Human Genetics, Vol. 60, No. 9, 29.09.2015, p. 525-531.

Research output: Contribution to journalArticle

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T1 - Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population

AU - Aiba, Yoshihiro

AU - Yamazaki, Keiko

AU - Nishida, Nao

AU - Kawashima, Minae

AU - Hitomi, Yuki

AU - Nakamura, Hitomi

AU - Komori, Atsumasa

AU - Fuyuno, Yuta

AU - Takahashi, Atsushi

AU - Kawaguchi, Takaaki

AU - Takazoe, Masakazu

AU - Suzuki, Yasuo

AU - Motoya, Satoshi

AU - Matsui, Toshiyuki

AU - Esaki, Motohiro

AU - Matsumoto, Takayuki

AU - Kubo, Michiaki

AU - Tokunaga, Katsushi

AU - Nakamura, Minoru

PY - 2015/9/29

Y1 - 2015/9/29

N2 - We previously identified TNFSF15 as the most significant susceptibility gene at non-HLA loci for both primary biliary cirrhosis (PBC) and Crohn's diseases (CD) in the Japanese population. The aim of this study is to identify further disease susceptibility genes shared by PBC and CD. We selected 15 and 33 genetic variants that were significantly associated with PBC and CD, respectively, based on previously reported genome-wide association studies of the Japanese population. Next, an association study was independently performed for these genetic variants in CD (1312 CD patients and 3331 healthy controls) and PBC (1279 PBC patients and 1015 healthy controls) cohorts. Two CD susceptibility genes, ICOSLG rs2838519 and IL12B rs6556412, were also nominally associated with susceptibility to PBC (P=3.85 × 10 -2 and P=8.40 × 10 -3, respectively). Three PBC susceptibility genes, CXCR5 rs6421571, STAT4 rs7574865 and NFKB1 rs230534, were nominally associated with susceptibility to CD (P=2.82 × 10 -2, P=3.88 × 10 -2 and P=2.04 × 10 -2, respectively). The effect of ICOSLG and CXCR5 variants were concordant but the effect of STAT4, NFKB1 and IL12B variants were discordant for PBC and CD. TNFSF15 and ICOSLG-CXCR5 might constitute a shared pathogenic pathway in the development of PBC and CD in the Japanese population, whereas IL12B-STAT4-NFKB1 might constitute an opposite pathogenic pathway, reflecting the different balance between Th1 and Th17 in the two diseases.

AB - We previously identified TNFSF15 as the most significant susceptibility gene at non-HLA loci for both primary biliary cirrhosis (PBC) and Crohn's diseases (CD) in the Japanese population. The aim of this study is to identify further disease susceptibility genes shared by PBC and CD. We selected 15 and 33 genetic variants that were significantly associated with PBC and CD, respectively, based on previously reported genome-wide association studies of the Japanese population. Next, an association study was independently performed for these genetic variants in CD (1312 CD patients and 3331 healthy controls) and PBC (1279 PBC patients and 1015 healthy controls) cohorts. Two CD susceptibility genes, ICOSLG rs2838519 and IL12B rs6556412, were also nominally associated with susceptibility to PBC (P=3.85 × 10 -2 and P=8.40 × 10 -3, respectively). Three PBC susceptibility genes, CXCR5 rs6421571, STAT4 rs7574865 and NFKB1 rs230534, were nominally associated with susceptibility to CD (P=2.82 × 10 -2, P=3.88 × 10 -2 and P=2.04 × 10 -2, respectively). The effect of ICOSLG and CXCR5 variants were concordant but the effect of STAT4, NFKB1 and IL12B variants were discordant for PBC and CD. TNFSF15 and ICOSLG-CXCR5 might constitute a shared pathogenic pathway in the development of PBC and CD in the Japanese population, whereas IL12B-STAT4-NFKB1 might constitute an opposite pathogenic pathway, reflecting the different balance between Th1 and Th17 in the two diseases.

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