A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals
Abstract Background and Aims Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the...
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creator | Kakuta, Yoichi Kawai, Yosuke Naito, Takeo Hirano, Atsushi Umeno, Junji Fuyuno, Yuta Liu, Zhenqiu Li, Dalin Nakano, Takeru Izumiyama, Yasuhiro Ichikawa, Ryo Okamoto, Daisuke Nagai, Hiroshi Matsumoto, Shin Yamamoto, Katsutoshi Yokoyama, Naonobu Chiba, Hirofumi Shimoyama, Yusuke Onodera, Motoyuki Moroi, Rintaro Kuroha, Masatake Kanazawa, Yoshitake Kimura, Tomoya Shiga, Hisashi Endo, Katsuya Negoro, Kenichi Yasuda, Jun Esaki, Motohiro Tokunaga, Katsushi Nakamura, Minoru Matsumoto, Takayuki McGovern, Dermot P B Nagasaki, Masao Kinouchi, Yoshitaka Shimosegawa, Tooru Masamune, Atsushi |
description | Abstract
Background and Aims
Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel.
Methods
Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions.
Results
Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10−26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10−19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p |
doi_str_mv | 10.1093/ecco-jcc/jjy197 |
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fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7458277</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/ecco-jcc/jjy197</oup_id><sourcerecordid>2149023993</sourcerecordid><originalsourceid>FETCH-LOGICAL-c494t-3140248bf5f49e7315b1397f9edcb1393abf77ac09075fc8108c47dd2e0c553</originalsourceid><addsrcrecordid>eNptkcFu1DAURS1ERUthzQ55iZDSsWO7jjdI0QBlqgoQw95ynOfWo4wd4mRQNojf4Pf4EjydUhWJ1buS7zt-VxehF5ScUaLYAqyNxcbaxWYzUyUfoRNayfOCc6ke32pWKMXPj9HTlDaECCVk9QQdMyIIqSQ_QT9qfAEhbqH47lvAdUrRejP6GPB6nNoZr1oIo3ezD9f4S_2Z1tgkbPDHuIMOr6dkoR994zs_znsSYBcHvBziTfj981fCb30CkwD7gC9NbwJkvQqt3_l2Ml16ho5cHvD8bp6i9ft3X5cfiqtPF6tlfVVYrvhYMMpJyavGCccVSEZFQ5mSTkFr94qZxklpLFFECmcrSirLZduWQKwQ7BS9OVD7qdnmlZxoMJ3uB781w6yj8frfl-Bv9HXcaclFVUqZAa_uAEP8NkEa9dbn5F2XA8Up6ZJyRUqmFMvWxcFqh5jSAO7-G0r0vjO970znzvShs7zx8uF19_6_JWXD64MhTv1_acUD2h8hS6aE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2149023993</pqid></control><display><type>article</type><title>A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Kakuta, Yoichi ; Kawai, Yosuke ; Naito, Takeo ; Hirano, Atsushi ; Umeno, Junji ; Fuyuno, Yuta ; Liu, Zhenqiu ; Li, Dalin ; Nakano, Takeru ; Izumiyama, Yasuhiro ; Ichikawa, Ryo ; Okamoto, Daisuke ; Nagai, Hiroshi ; Matsumoto, Shin ; Yamamoto, Katsutoshi ; Yokoyama, Naonobu ; Chiba, Hirofumi ; Shimoyama, Yusuke ; Onodera, Motoyuki ; Moroi, Rintaro ; Kuroha, Masatake ; Kanazawa, Yoshitake ; Kimura, Tomoya ; Shiga, Hisashi ; Endo, Katsuya ; Negoro, Kenichi ; Yasuda, Jun ; Esaki, Motohiro ; Tokunaga, Katsushi ; Nakamura, Minoru ; Matsumoto, Takayuki ; McGovern, Dermot P B ; Nagasaki, Masao ; Kinouchi, Yoshitaka ; Shimosegawa, Tooru ; Masamune, Atsushi</creator><creatorcontrib>Kakuta, Yoichi ; Kawai, Yosuke ; Naito, Takeo ; Hirano, Atsushi ; Umeno, Junji ; Fuyuno, Yuta ; Liu, Zhenqiu ; Li, Dalin ; Nakano, Takeru ; Izumiyama, Yasuhiro ; Ichikawa, Ryo ; Okamoto, Daisuke ; Nagai, Hiroshi ; Matsumoto, Shin ; Yamamoto, Katsutoshi ; Yokoyama, Naonobu ; Chiba, Hirofumi ; Shimoyama, Yusuke ; Onodera, Motoyuki ; Moroi, Rintaro ; Kuroha, Masatake ; Kanazawa, Yoshitake ; Kimura, Tomoya ; Shiga, Hisashi ; Endo, Katsuya ; Negoro, Kenichi ; Yasuda, Jun ; Esaki, Motohiro ; Tokunaga, Katsushi ; Nakamura, Minoru ; Matsumoto, Takayuki ; McGovern, Dermot P B ; Nagasaki, Masao ; Kinouchi, Yoshitaka ; Shimosegawa, Tooru ; Masamune, Atsushi</creatorcontrib><description>Abstract
Background and Aims
Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel.
Methods
Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions.
Results
Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10−26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10−19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10−6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10−8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression.
Conclusions
RAP1A is a novel susceptibility locus for CD in the Japanese population.</description><identifier>ISSN: 1873-9946</identifier><identifier>EISSN: 1876-4479</identifier><identifier>DOI: 10.1093/ecco-jcc/jjy197</identifier><identifier>PMID: 30500874</identifier><language>eng</language><publisher>UK: Oxford University Press</publisher><subject>Adult ; Case-Control Studies ; Crohn Disease - epidemiology ; Crohn Disease - genetics ; Female ; Gene Expression Profiling ; Genetic Predisposition to Disease - genetics ; Genome-Wide Association Study ; Humans ; Japan - epidemiology ; Male ; Original ; Polymorphism, Single Nucleotide - genetics ; rap1 GTP-Binding Proteins - genetics ; rap1 GTP-Binding Proteins - physiology ; Young Adult</subject><ispartof>Journal of Crohn's and colitis, 2019-04, Vol.13 (5), p.648-658</ispartof><rights>Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.
For permissions, please email: journals.permissions@oup.com 2018</rights><rights>Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved.
For permissions, please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c494t-3140248bf5f49e7315b1397f9edcb1393abf77ac09075fc8108c47dd2e0c553</citedby><cites>FETCH-LOGICAL-c494t-3140248bf5f49e7315b1397f9edcb1393abf77ac09075fc8108c47dd2e0c553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30500874$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kakuta, Yoichi</creatorcontrib><creatorcontrib>Kawai, Yosuke</creatorcontrib><creatorcontrib>Naito, Takeo</creatorcontrib><creatorcontrib>Hirano, Atsushi</creatorcontrib><creatorcontrib>Umeno, Junji</creatorcontrib><creatorcontrib>Fuyuno, Yuta</creatorcontrib><creatorcontrib>Liu, Zhenqiu</creatorcontrib><creatorcontrib>Li, Dalin</creatorcontrib><creatorcontrib>Nakano, Takeru</creatorcontrib><creatorcontrib>Izumiyama, Yasuhiro</creatorcontrib><creatorcontrib>Ichikawa, Ryo</creatorcontrib><creatorcontrib>Okamoto, Daisuke</creatorcontrib><creatorcontrib>Nagai, Hiroshi</creatorcontrib><creatorcontrib>Matsumoto, Shin</creatorcontrib><creatorcontrib>Yamamoto, Katsutoshi</creatorcontrib><creatorcontrib>Yokoyama, Naonobu</creatorcontrib><creatorcontrib>Chiba, Hirofumi</creatorcontrib><creatorcontrib>Shimoyama, Yusuke</creatorcontrib><creatorcontrib>Onodera, Motoyuki</creatorcontrib><creatorcontrib>Moroi, Rintaro</creatorcontrib><creatorcontrib>Kuroha, Masatake</creatorcontrib><creatorcontrib>Kanazawa, Yoshitake</creatorcontrib><creatorcontrib>Kimura, Tomoya</creatorcontrib><creatorcontrib>Shiga, Hisashi</creatorcontrib><creatorcontrib>Endo, Katsuya</creatorcontrib><creatorcontrib>Negoro, Kenichi</creatorcontrib><creatorcontrib>Yasuda, Jun</creatorcontrib><creatorcontrib>Esaki, Motohiro</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><creatorcontrib>Nakamura, Minoru</creatorcontrib><creatorcontrib>Matsumoto, Takayuki</creatorcontrib><creatorcontrib>McGovern, Dermot P B</creatorcontrib><creatorcontrib>Nagasaki, Masao</creatorcontrib><creatorcontrib>Kinouchi, Yoshitaka</creatorcontrib><creatorcontrib>Shimosegawa, Tooru</creatorcontrib><creatorcontrib>Masamune, Atsushi</creatorcontrib><title>A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals</title><title>Journal of Crohn's and colitis</title><addtitle>J Crohns Colitis</addtitle><description>Abstract
Background and Aims
Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel.
Methods
Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions.
Results
Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10−26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10−19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10−6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10−8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression.
Conclusions
RAP1A is a novel susceptibility locus for CD in the Japanese population.</description><subject>Adult</subject><subject>Case-Control Studies</subject><subject>Crohn Disease - epidemiology</subject><subject>Crohn Disease - genetics</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Japan - epidemiology</subject><subject>Male</subject><subject>Original</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>rap1 GTP-Binding Proteins - genetics</subject><subject>rap1 GTP-Binding Proteins - physiology</subject><subject>Young Adult</subject><issn>1873-9946</issn><issn>1876-4479</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkcFu1DAURS1ERUthzQ55iZDSsWO7jjdI0QBlqgoQw95ynOfWo4wd4mRQNojf4Pf4EjydUhWJ1buS7zt-VxehF5ScUaLYAqyNxcbaxWYzUyUfoRNayfOCc6ke32pWKMXPj9HTlDaECCVk9QQdMyIIqSQ_QT9qfAEhbqH47lvAdUrRejP6GPB6nNoZr1oIo3ezD9f4S_2Z1tgkbPDHuIMOr6dkoR994zs_znsSYBcHvBziTfj981fCb30CkwD7gC9NbwJkvQqt3_l2Ml16ho5cHvD8bp6i9ft3X5cfiqtPF6tlfVVYrvhYMMpJyavGCccVSEZFQ5mSTkFr94qZxklpLFFECmcrSirLZduWQKwQ7BS9OVD7qdnmlZxoMJ3uB781w6yj8frfl-Bv9HXcaclFVUqZAa_uAEP8NkEa9dbn5F2XA8Up6ZJyRUqmFMvWxcFqh5jSAO7-G0r0vjO970znzvShs7zx8uF19_6_JWXD64MhTv1_acUD2h8hS6aE</recordid><startdate>20190426</startdate><enddate>20190426</enddate><creator>Kakuta, Yoichi</creator><creator>Kawai, Yosuke</creator><creator>Naito, Takeo</creator><creator>Hirano, Atsushi</creator><creator>Umeno, Junji</creator><creator>Fuyuno, Yuta</creator><creator>Liu, Zhenqiu</creator><creator>Li, Dalin</creator><creator>Nakano, Takeru</creator><creator>Izumiyama, Yasuhiro</creator><creator>Ichikawa, Ryo</creator><creator>Okamoto, Daisuke</creator><creator>Nagai, Hiroshi</creator><creator>Matsumoto, Shin</creator><creator>Yamamoto, Katsutoshi</creator><creator>Yokoyama, Naonobu</creator><creator>Chiba, Hirofumi</creator><creator>Shimoyama, Yusuke</creator><creator>Onodera, Motoyuki</creator><creator>Moroi, Rintaro</creator><creator>Kuroha, Masatake</creator><creator>Kanazawa, Yoshitake</creator><creator>Kimura, Tomoya</creator><creator>Shiga, Hisashi</creator><creator>Endo, Katsuya</creator><creator>Negoro, Kenichi</creator><creator>Yasuda, Jun</creator><creator>Esaki, Motohiro</creator><creator>Tokunaga, Katsushi</creator><creator>Nakamura, Minoru</creator><creator>Matsumoto, Takayuki</creator><creator>McGovern, Dermot P B</creator><creator>Nagasaki, Masao</creator><creator>Kinouchi, Yoshitaka</creator><creator>Shimosegawa, Tooru</creator><creator>Masamune, Atsushi</creator><general>Oxford University Press</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20190426</creationdate><title>A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals</title><author>Kakuta, Yoichi ; Kawai, Yosuke ; Naito, Takeo ; Hirano, Atsushi ; Umeno, Junji ; Fuyuno, Yuta ; Liu, Zhenqiu ; Li, Dalin ; Nakano, Takeru ; Izumiyama, Yasuhiro ; Ichikawa, Ryo ; Okamoto, Daisuke ; Nagai, Hiroshi ; Matsumoto, Shin ; Yamamoto, Katsutoshi ; Yokoyama, Naonobu ; Chiba, Hirofumi ; Shimoyama, Yusuke ; Onodera, Motoyuki ; Moroi, Rintaro ; Kuroha, Masatake ; Kanazawa, Yoshitake ; Kimura, Tomoya ; Shiga, Hisashi ; Endo, Katsuya ; Negoro, Kenichi ; Yasuda, Jun ; Esaki, Motohiro ; Tokunaga, Katsushi ; Nakamura, Minoru ; Matsumoto, Takayuki ; McGovern, Dermot P B ; Nagasaki, Masao ; Kinouchi, Yoshitaka ; Shimosegawa, Tooru ; Masamune, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c494t-3140248bf5f49e7315b1397f9edcb1393abf77ac09075fc8108c47dd2e0c553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Adult</topic><topic>Case-Control Studies</topic><topic>Crohn Disease - epidemiology</topic><topic>Crohn Disease - genetics</topic><topic>Female</topic><topic>Gene Expression Profiling</topic><topic>Genetic Predisposition to Disease - genetics</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Japan - epidemiology</topic><topic>Male</topic><topic>Original</topic><topic>Polymorphism, Single Nucleotide - genetics</topic><topic>rap1 GTP-Binding Proteins - genetics</topic><topic>rap1 GTP-Binding Proteins - physiology</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kakuta, Yoichi</creatorcontrib><creatorcontrib>Kawai, Yosuke</creatorcontrib><creatorcontrib>Naito, Takeo</creatorcontrib><creatorcontrib>Hirano, Atsushi</creatorcontrib><creatorcontrib>Umeno, Junji</creatorcontrib><creatorcontrib>Fuyuno, Yuta</creatorcontrib><creatorcontrib>Liu, Zhenqiu</creatorcontrib><creatorcontrib>Li, Dalin</creatorcontrib><creatorcontrib>Nakano, Takeru</creatorcontrib><creatorcontrib>Izumiyama, Yasuhiro</creatorcontrib><creatorcontrib>Ichikawa, Ryo</creatorcontrib><creatorcontrib>Okamoto, Daisuke</creatorcontrib><creatorcontrib>Nagai, Hiroshi</creatorcontrib><creatorcontrib>Matsumoto, Shin</creatorcontrib><creatorcontrib>Yamamoto, Katsutoshi</creatorcontrib><creatorcontrib>Yokoyama, Naonobu</creatorcontrib><creatorcontrib>Chiba, Hirofumi</creatorcontrib><creatorcontrib>Shimoyama, Yusuke</creatorcontrib><creatorcontrib>Onodera, Motoyuki</creatorcontrib><creatorcontrib>Moroi, Rintaro</creatorcontrib><creatorcontrib>Kuroha, Masatake</creatorcontrib><creatorcontrib>Kanazawa, Yoshitake</creatorcontrib><creatorcontrib>Kimura, Tomoya</creatorcontrib><creatorcontrib>Shiga, Hisashi</creatorcontrib><creatorcontrib>Endo, Katsuya</creatorcontrib><creatorcontrib>Negoro, Kenichi</creatorcontrib><creatorcontrib>Yasuda, Jun</creatorcontrib><creatorcontrib>Esaki, Motohiro</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><creatorcontrib>Nakamura, Minoru</creatorcontrib><creatorcontrib>Matsumoto, Takayuki</creatorcontrib><creatorcontrib>McGovern, Dermot P B</creatorcontrib><creatorcontrib>Nagasaki, Masao</creatorcontrib><creatorcontrib>Kinouchi, Yoshitaka</creatorcontrib><creatorcontrib>Shimosegawa, Tooru</creatorcontrib><creatorcontrib>Masamune, Atsushi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of Crohn's and colitis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kakuta, Yoichi</au><au>Kawai, Yosuke</au><au>Naito, Takeo</au><au>Hirano, Atsushi</au><au>Umeno, Junji</au><au>Fuyuno, Yuta</au><au>Liu, Zhenqiu</au><au>Li, Dalin</au><au>Nakano, Takeru</au><au>Izumiyama, Yasuhiro</au><au>Ichikawa, Ryo</au><au>Okamoto, Daisuke</au><au>Nagai, Hiroshi</au><au>Matsumoto, Shin</au><au>Yamamoto, Katsutoshi</au><au>Yokoyama, Naonobu</au><au>Chiba, Hirofumi</au><au>Shimoyama, Yusuke</au><au>Onodera, Motoyuki</au><au>Moroi, Rintaro</au><au>Kuroha, Masatake</au><au>Kanazawa, Yoshitake</au><au>Kimura, Tomoya</au><au>Shiga, Hisashi</au><au>Endo, Katsuya</au><au>Negoro, Kenichi</au><au>Yasuda, Jun</au><au>Esaki, Motohiro</au><au>Tokunaga, Katsushi</au><au>Nakamura, Minoru</au><au>Matsumoto, Takayuki</au><au>McGovern, Dermot P B</au><au>Nagasaki, Masao</au><au>Kinouchi, Yoshitaka</au><au>Shimosegawa, Tooru</au><au>Masamune, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals</atitle><jtitle>Journal of Crohn's and colitis</jtitle><addtitle>J Crohns Colitis</addtitle><date>2019-04-26</date><risdate>2019</risdate><volume>13</volume><issue>5</issue><spage>648</spage><epage>658</epage><pages>648-658</pages><issn>1873-9946</issn><eissn>1876-4479</eissn><abstract>Abstract
Background and Aims
Genome-wide association studies [GWASs] of European populations have identified numerous susceptibility loci for Crohn’s disease [CD]. Susceptibility genes differ by ethnicity, however, so GWASs specific for Asian populations are required. This study aimed to clarify the Japanese-specific genetic background for CD by a GWAS using the Japonica array [JPA] and subsequent imputation with the 1KJPN reference panel.
Methods
Two independent Japanese case/control sets (Tohoku region [379 CD patients, 1621 controls] and Kyushu region [334 CD patients, 462 controls]) were included. GWASs were performed separately for each population, followed by a meta-analysis. Two additional replication sets [254 + 516 CD patients and 287 + 565 controls] were analysed for top hit single nucleotide polymorphisms [SNPs] from novel genomic regions.
Results
Genotype data of 4 335 144 SNPs from 713 Japanese CD patients and 2083 controls were analysed. SNPs located in TNFSF15 (rs78898421, Pmeta = 2.59 × 10−26, odds ratio [OR] = 2.10), HLA-DQB1 [rs184950714, pmeta = 3.56 × 10−19, OR = 2.05], ZNF365, and 4p14 loci were significantly associated with CD in Japanese individuals. Replication analyses were performed for four novel candidate loci [p <1 × 10−6], and rs488200 located upstream of RAP1A was significantly associated with CD [pcombined = 4.36 × 10−8, OR = 1.31]. Transcriptome analysis of CD4+ effector memory T cells from lamina propria mononuclear cells of CD patients revealed a significant association of rs488200 with RAP1A expression.
Conclusions
RAP1A is a novel susceptibility locus for CD in the Japanese population.</abstract><cop>UK</cop><pub>Oxford University Press</pub><pmid>30500874</pmid><doi>10.1093/ecco-jcc/jjy197</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection |
subjects | Adult Case-Control Studies Crohn Disease - epidemiology Crohn Disease - genetics Female Gene Expression Profiling Genetic Predisposition to Disease - genetics Genome-Wide Association Study Humans Japan - epidemiology Male Original Polymorphism, Single Nucleotide - genetics rap1 GTP-Binding Proteins - genetics rap1 GTP-Binding Proteins - physiology Young Adult |
title | A Genome-wide Association Study Identifying RAP1A as a Novel Susceptibility Gene for Crohn’s Disease in Japanese Individuals |
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