title: Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population.
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.
authors.affiliation: Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Omura, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Aiba
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Science, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: Nao
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Minae
authors.initials: M
authors.lastname: Kawashima
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hitomi
authors.affiliation: Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Omura, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Komori
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Science, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.|Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Fuyuno
authors.affiliation: Laboratory for Statistical Analysis, Center for Integrative Medical Sciences, RIKEN, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.affiliation: Department of Medicine, Division of Gastroenterology, Tokyo Yamate Medical Center, Tokyo, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kawaguchi
authors.affiliation: Department of Medicine, Division of Gastroenterology, Tokyo Yamate Medical Center, Tokyo, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Takazoe
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Toho University, Chiba, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Gastroenterology, Sapporo Kosei Hospital, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Motoya
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Science, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.|Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Esaki
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Iwate Medical University, Iwate, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Laboratory for Genotyping Development, Center for Integrative Medical Science, Institute of Physical and Chemical Research (RIKEN), Yokohama, Japan.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Katsushi
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Clinical Research Center, National Hospital Organization, Nagasaki Medical Center, Omura, Japan.|Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Headquarters of PBC Research in the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ) and gp210 working in Research Program of Intractable Hepatoboliary Disease Study Group supported by the Ministry of Health, Labour, and Welfare of Japan, Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Nagasaki, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008105:Liver Cirrhosis, Biliary / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult