Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population
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...
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| Veröffentlicht in: | Journal of human genetics 2015-09, Vol.60 (9), p.525-531 |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1038/jhg.2015.59 |
| format | Article |
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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.</description><identifier>ISSN: 1434-5161</identifier><identifier>EISSN: 1435-232X</identifier><identifier>DOI: 10.1038/jhg.2015.59</identifier><identifier>PMID: 26084578</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group - genetics ; Asian Continental Ancestry Group - statistics & numerical data ; Bile ; Cirrhosis ; Crohn Disease - epidemiology ; Crohn Disease - genetics ; Crohn's disease ; CXCR5 protein ; Disease ; Female ; Genetic diversity ; Genetic Predisposition to Disease - genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Helper cells ; Histocompatibility antigen HLA ; Humans ; Interleukin 1 ; Japan - epidemiology ; Liver cirrhosis ; Liver Cirrhosis, Biliary - epidemiology ; Liver Cirrhosis, Biliary - genetics ; Lymphocytes T ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Population ; Population studies ; Primary biliary cirrhosis ; Stat4 protein ; Susceptibility ; Young Adult</subject><ispartof>Journal of human genetics, 2015-09, Vol.60 (9), p.525-531</ispartof><rights>Copyright Nature Publishing Group Sep 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c439t-5a57b8ad8d086cc52b049fda7b9b1f7389b350df6eb54a86bf90598576b7653f3</citedby><cites>FETCH-LOGICAL-c439t-5a57b8ad8d086cc52b049fda7b9b1f7389b350df6eb54a86bf90598576b7653f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26084578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aiba, Yoshihiro</creatorcontrib><creatorcontrib>Yamazaki, Keiko</creatorcontrib><creatorcontrib>Nishida, Nao</creatorcontrib><creatorcontrib>Kawashima, Minae</creatorcontrib><creatorcontrib>Hitomi, Yuki</creatorcontrib><creatorcontrib>Nakamura, Hitomi</creatorcontrib><creatorcontrib>Komori, Atsumasa</creatorcontrib><creatorcontrib>Fuyuno, Yuta</creatorcontrib><creatorcontrib>Takahashi, Atsushi</creatorcontrib><creatorcontrib>Kawaguchi, Takaaki</creatorcontrib><creatorcontrib>Takazoe, Masakazu</creatorcontrib><creatorcontrib>Suzuki, Yasuo</creatorcontrib><creatorcontrib>Motoya, Satoshi</creatorcontrib><creatorcontrib>Matsui, Toshiyuki</creatorcontrib><creatorcontrib>Esaki, Motohiro</creatorcontrib><creatorcontrib>Matsumoto, Takayuki</creatorcontrib><creatorcontrib>Kubo, Michiaki</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><creatorcontrib>Nakamura, Minoru</creatorcontrib><title>Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population</title><title>Journal of human genetics</title><addtitle>J Hum Genet</addtitle><description>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.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Asian Continental Ancestry Group - genetics</subject><subject>Asian Continental Ancestry Group - statistics & numerical data</subject><subject>Bile</subject><subject>Cirrhosis</subject><subject>Crohn Disease - epidemiology</subject><subject>Crohn Disease - genetics</subject><subject>Crohn's disease</subject><subject>CXCR5 protein</subject><subject>Disease</subject><subject>Female</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Helper cells</subject><subject>Histocompatibility antigen HLA</subject><subject>Humans</subject><subject>Interleukin 1</subject><subject>Japan - epidemiology</subject><subject>Liver cirrhosis</subject><subject>Liver Cirrhosis, Biliary - epidemiology</subject><subject>Liver Cirrhosis, Biliary - genetics</subject><subject>Lymphocytes T</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population</subject><subject>Population studies</subject><subject>Primary biliary cirrhosis</subject><subject>Stat4 protein</subject><subject>Susceptibility</subject><subject>Young Adult</subject><issn>1434-5161</issn><issn>1435-232X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNqN0c1r2zAYBnBRWpo066n3IehhheJM35aOI1s_RmCXFXoTki3XCo7lSvYh_32VNe1hh9LTK9CPB716ALjAaIkRld837dOSIMyXXB2BOWaUF4SSx-N_Z1ZwLPAMnKW0QQhRUpJTMCMCScZLOQfhp0_OJAfTlCo3jN76zo87-OR6l2BqTXQ1tDs4RL81cQf31_tZ-RjbkHyCpq_hKoa2_5ZgfQjzPRxbB3-bweQYB4cwTJ0Zfei_gJPGdMmdH-YCPNz8-ru6K9Z_bu9XP9ZFxagaC254aaWpZY2kqCpOLGKqqU1plcVNSaWylKO6Ec5yZqSwjUJcSV4KWwpOG7oAV6-5QwzPk0uj3vq8YNflB4UpaZyZkkQy-QmKhWIUCZLp5X90E6bY50U0oRQLipD6UGHJWEkklSyr61dVxZBSdI0-_LHGSO-L1blYvS9Wc5X110PmZLeufrdvTdIXoKGdxQ</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Aiba, Yoshihiro</creator><creator>Yamazaki, Keiko</creator><creator>Nishida, Nao</creator><creator>Kawashima, Minae</creator><creator>Hitomi, Yuki</creator><creator>Nakamura, Hitomi</creator><creator>Komori, Atsumasa</creator><creator>Fuyuno, Yuta</creator><creator>Takahashi, Atsushi</creator><creator>Kawaguchi, Takaaki</creator><creator>Takazoe, Masakazu</creator><creator>Suzuki, Yasuo</creator><creator>Motoya, Satoshi</creator><creator>Matsui, Toshiyuki</creator><creator>Esaki, Motohiro</creator><creator>Matsumoto, Takayuki</creator><creator>Kubo, Michiaki</creator><creator>Tokunaga, Katsushi</creator><creator>Nakamura, Minoru</creator><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20150901</creationdate><title>Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c439t-5a57b8ad8d086cc52b049fda7b9b1f7389b350df6eb54a86bf90598576b7653f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Asian Continental Ancestry Group - 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Academic</collection><jtitle>Journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aiba, Yoshihiro</au><au>Yamazaki, Keiko</au><au>Nishida, Nao</au><au>Kawashima, Minae</au><au>Hitomi, Yuki</au><au>Nakamura, Hitomi</au><au>Komori, Atsumasa</au><au>Fuyuno, Yuta</au><au>Takahashi, Atsushi</au><au>Kawaguchi, Takaaki</au><au>Takazoe, Masakazu</au><au>Suzuki, Yasuo</au><au>Motoya, Satoshi</au><au>Matsui, Toshiyuki</au><au>Esaki, Motohiro</au><au>Matsumoto, Takayuki</au><au>Kubo, Michiaki</au><au>Tokunaga, Katsushi</au><au>Nakamura, Minoru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population</atitle><jtitle>Journal of human genetics</jtitle><addtitle>J Hum Genet</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>60</volume><issue>9</issue><spage>525</spage><epage>531</epage><pages>525-531</pages><issn>1434-5161</issn><eissn>1435-232X</eissn><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.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>26084578</pmid><doi>10.1038/jhg.2015.59</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Aged Aged, 80 and over Asian Continental Ancestry Group - genetics Asian Continental Ancestry Group - statistics & numerical data Bile Cirrhosis Crohn Disease - epidemiology Crohn Disease - genetics Crohn's disease CXCR5 protein Disease Female Genetic diversity Genetic Predisposition to Disease - genetics Genome-wide association studies Genome-Wide Association Study Genomes Helper cells Histocompatibility antigen HLA Humans Interleukin 1 Japan - epidemiology Liver cirrhosis Liver Cirrhosis, Biliary - epidemiology Liver Cirrhosis, Biliary - genetics Lymphocytes T Male Middle Aged Polymorphism, Single Nucleotide Population Population studies Primary biliary cirrhosis Stat4 protein Susceptibility Young Adult |
| title | Disease susceptibility genes shared by primary biliary cirrhosis and Crohn's disease in the Japanese population |
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