New susceptibility variants to narcolepsy identified in HLA class II region
Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are need...
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| Veröffentlicht in: | Human molecular genetics 2015-02, Vol.24 (3), p.891-898 |
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| creator | Miyagawa, Taku Toyoda, Hiromi Hirataka, Akane Kanbayashi, Takashi Imanishi, Aya Sagawa, Yohei Kotorii, Nozomu Kotorii, Tatayu Hashizume, Yuji Ogi, Kimihiro Hiejima, Hiroshi Kamei, Yuichi Hida, Akiko Miyamoto, Masayuki Imai, Makoto Fujimura, Yota Tamura, Yoshiyuki Ikegami, Azusa Wada, Yamato Moriya, Shunpei Furuya, Hirokazu Kato, Mitsuhiro Omata, Naoto Kojima, Hiroto Kashiwase, Koichi Saji, Hiroh Khor, Seik-Soon Yamasaki, Maria Wada, Yuji Ishigooka, Jun Kuroda, Kenji Kume, Kazuhiko Chiba, Shigeru Yamada, Naoto Okawa, Masako Hirata, Koichi Uchimura, Naohisa Shimizu, Tetsuo Inoue, Yuichi Honda, Yutaka Mishima, Kazuo Honda, Makoto Tokunaga, Katsushi |
| description | Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy. |
| doi_str_mv | 10.1093/hmg/ddu480 |
| format | Article |
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DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.</description><identifier>ISSN: 0964-6906</identifier><identifier>EISSN: 1460-2083</identifier><identifier>DOI: 10.1093/hmg/ddu480</identifier><identifier>PMID: 25256355</identifier><language>eng</language><publisher>England</publisher><subject>Asian Continental Ancestry Group - genetics ; Genes, MHC Class II ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genetic Variation ; HLA-DP beta-Chains - genetics ; HLA-DQ beta-Chains - genetics ; Humans ; Japan ; Narcolepsy - genetics</subject><ispartof>Human molecular genetics, 2015-02, Vol.24 (3), p.891-898</ispartof><rights>The Author 2014. 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-c389t-4356d9eeff27b988b82c765ea12108fc6daa41909224f5a6d5c88af1f43cc2943</citedby><cites>FETCH-LOGICAL-c389t-4356d9eeff27b988b82c765ea12108fc6daa41909224f5a6d5c88af1f43cc2943</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/25256355$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Miyagawa, Taku</creatorcontrib><creatorcontrib>Toyoda, Hiromi</creatorcontrib><creatorcontrib>Hirataka, Akane</creatorcontrib><creatorcontrib>Kanbayashi, Takashi</creatorcontrib><creatorcontrib>Imanishi, Aya</creatorcontrib><creatorcontrib>Sagawa, Yohei</creatorcontrib><creatorcontrib>Kotorii, Nozomu</creatorcontrib><creatorcontrib>Kotorii, Tatayu</creatorcontrib><creatorcontrib>Hashizume, Yuji</creatorcontrib><creatorcontrib>Ogi, Kimihiro</creatorcontrib><creatorcontrib>Hiejima, Hiroshi</creatorcontrib><creatorcontrib>Kamei, Yuichi</creatorcontrib><creatorcontrib>Hida, Akiko</creatorcontrib><creatorcontrib>Miyamoto, Masayuki</creatorcontrib><creatorcontrib>Imai, Makoto</creatorcontrib><creatorcontrib>Fujimura, Yota</creatorcontrib><creatorcontrib>Tamura, Yoshiyuki</creatorcontrib><creatorcontrib>Ikegami, Azusa</creatorcontrib><creatorcontrib>Wada, Yamato</creatorcontrib><creatorcontrib>Moriya, Shunpei</creatorcontrib><creatorcontrib>Furuya, Hirokazu</creatorcontrib><creatorcontrib>Kato, Mitsuhiro</creatorcontrib><creatorcontrib>Omata, Naoto</creatorcontrib><creatorcontrib>Kojima, Hiroto</creatorcontrib><creatorcontrib>Kashiwase, Koichi</creatorcontrib><creatorcontrib>Saji, Hiroh</creatorcontrib><creatorcontrib>Khor, Seik-Soon</creatorcontrib><creatorcontrib>Yamasaki, Maria</creatorcontrib><creatorcontrib>Wada, Yuji</creatorcontrib><creatorcontrib>Ishigooka, Jun</creatorcontrib><creatorcontrib>Kuroda, Kenji</creatorcontrib><creatorcontrib>Kume, Kazuhiko</creatorcontrib><creatorcontrib>Chiba, Shigeru</creatorcontrib><creatorcontrib>Yamada, Naoto</creatorcontrib><creatorcontrib>Okawa, Masako</creatorcontrib><creatorcontrib>Hirata, Koichi</creatorcontrib><creatorcontrib>Uchimura, Naohisa</creatorcontrib><creatorcontrib>Shimizu, Tetsuo</creatorcontrib><creatorcontrib>Inoue, Yuichi</creatorcontrib><creatorcontrib>Honda, Yutaka</creatorcontrib><creatorcontrib>Mishima, Kazuo</creatorcontrib><creatorcontrib>Honda, Makoto</creatorcontrib><creatorcontrib>Tokunaga, Katsushi</creatorcontrib><title>New susceptibility variants to narcolepsy identified in HLA class II region</title><title>Human molecular genetics</title><addtitle>Hum Mol Genet</addtitle><description>Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.</description><subject>Asian Continental Ancestry Group - genetics</subject><subject>Genes, MHC Class II</subject><subject>Genetic Association Studies</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic Variation</subject><subject>HLA-DP beta-Chains - genetics</subject><subject>HLA-DQ beta-Chains - genetics</subject><subject>Humans</subject><subject>Japan</subject><subject>Narcolepsy - genetics</subject><issn>0964-6906</issn><issn>1460-2083</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtKAzEARYMotlY3foBkKcLYvCdZllJtsehG10MmjxqZl8mM0r93pNXV3RwO3APANUb3GCk6f693c2sHJtEJmGImUEaQpKdgipRgmVBITMBFSh8IYcFofg4mhBMuKOdT8PTsvmEaknFdH8pQhX4Pv3QMuukT7FvY6GjaynVpD4N1TR98cBaGBq63C2gqnRLcbGB0u9A2l-DM6yq5q-POwNvD6nW5zrYvj5vlYpsZKlWfMcqFVc55T_JSSVlKYnLBncYEI-mNsFozrJAihHmuheVGSu2xZ9QYohidgduDt4vt5-BSX9RhPFBVunHtkAosOKF5jjAZ0bsDamKbUnS-6GKoddwXGBW_8YoxXnGIN8I3R-9Q1s7-o3-16A9OJmsY</recordid><startdate>20150201</startdate><enddate>20150201</enddate><creator>Miyagawa, Taku</creator><creator>Toyoda, Hiromi</creator><creator>Hirataka, Akane</creator><creator>Kanbayashi, Takashi</creator><creator>Imanishi, Aya</creator><creator>Sagawa, Yohei</creator><creator>Kotorii, Nozomu</creator><creator>Kotorii, Tatayu</creator><creator>Hashizume, Yuji</creator><creator>Ogi, Kimihiro</creator><creator>Hiejima, Hiroshi</creator><creator>Kamei, Yuichi</creator><creator>Hida, Akiko</creator><creator>Miyamoto, Masayuki</creator><creator>Imai, Makoto</creator><creator>Fujimura, Yota</creator><creator>Tamura, Yoshiyuki</creator><creator>Ikegami, Azusa</creator><creator>Wada, Yamato</creator><creator>Moriya, Shunpei</creator><creator>Furuya, Hirokazu</creator><creator>Kato, Mitsuhiro</creator><creator>Omata, Naoto</creator><creator>Kojima, Hiroto</creator><creator>Kashiwase, Koichi</creator><creator>Saji, Hiroh</creator><creator>Khor, Seik-Soon</creator><creator>Yamasaki, Maria</creator><creator>Wada, Yuji</creator><creator>Ishigooka, Jun</creator><creator>Kuroda, Kenji</creator><creator>Kume, Kazuhiko</creator><creator>Chiba, Shigeru</creator><creator>Yamada, Naoto</creator><creator>Okawa, Masako</creator><creator>Hirata, Koichi</creator><creator>Uchimura, Naohisa</creator><creator>Shimizu, Tetsuo</creator><creator>Inoue, Yuichi</creator><creator>Honda, Yutaka</creator><creator>Mishima, Kazuo</creator><creator>Honda, Makoto</creator><creator>Tokunaga, Katsushi</creator><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></search><sort><creationdate>20150201</creationdate><title>New susceptibility variants to narcolepsy identified in HLA class II region</title><author>Miyagawa, Taku ; Toyoda, Hiromi ; Hirataka, Akane ; Kanbayashi, Takashi ; Imanishi, Aya ; Sagawa, Yohei ; Kotorii, Nozomu ; Kotorii, Tatayu ; Hashizume, Yuji ; Ogi, Kimihiro ; Hiejima, Hiroshi ; Kamei, Yuichi ; Hida, Akiko ; Miyamoto, Masayuki ; Imai, Makoto ; Fujimura, Yota ; Tamura, Yoshiyuki ; Ikegami, Azusa ; Wada, Yamato ; Moriya, Shunpei ; Furuya, Hirokazu ; Kato, Mitsuhiro ; Omata, Naoto ; Kojima, Hiroto ; Kashiwase, Koichi ; Saji, Hiroh ; Khor, Seik-Soon ; Yamasaki, Maria ; Wada, Yuji ; Ishigooka, Jun ; Kuroda, Kenji ; Kume, Kazuhiko ; Chiba, Shigeru ; Yamada, Naoto ; Okawa, Masako ; Hirata, Koichi ; Uchimura, Naohisa ; Shimizu, Tetsuo ; Inoue, Yuichi ; Honda, Yutaka ; Mishima, Kazuo ; Honda, Makoto ; Tokunaga, Katsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c389t-4356d9eeff27b988b82c765ea12108fc6daa41909224f5a6d5c88af1f43cc2943</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Asian Continental Ancestry Group - 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Academic</collection><jtitle>Human molecular genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Miyagawa, Taku</au><au>Toyoda, Hiromi</au><au>Hirataka, Akane</au><au>Kanbayashi, Takashi</au><au>Imanishi, Aya</au><au>Sagawa, Yohei</au><au>Kotorii, Nozomu</au><au>Kotorii, Tatayu</au><au>Hashizume, Yuji</au><au>Ogi, Kimihiro</au><au>Hiejima, Hiroshi</au><au>Kamei, Yuichi</au><au>Hida, Akiko</au><au>Miyamoto, Masayuki</au><au>Imai, Makoto</au><au>Fujimura, Yota</au><au>Tamura, Yoshiyuki</au><au>Ikegami, Azusa</au><au>Wada, Yamato</au><au>Moriya, Shunpei</au><au>Furuya, Hirokazu</au><au>Kato, Mitsuhiro</au><au>Omata, Naoto</au><au>Kojima, Hiroto</au><au>Kashiwase, Koichi</au><au>Saji, Hiroh</au><au>Khor, Seik-Soon</au><au>Yamasaki, Maria</au><au>Wada, Yuji</au><au>Ishigooka, Jun</au><au>Kuroda, Kenji</au><au>Kume, Kazuhiko</au><au>Chiba, Shigeru</au><au>Yamada, Naoto</au><au>Okawa, Masako</au><au>Hirata, Koichi</au><au>Uchimura, Naohisa</au><au>Shimizu, Tetsuo</au><au>Inoue, Yuichi</au><au>Honda, Yutaka</au><au>Mishima, Kazuo</au><au>Honda, Makoto</au><au>Tokunaga, Katsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>New susceptibility variants to narcolepsy identified in HLA class II region</atitle><jtitle>Human molecular genetics</jtitle><addtitle>Hum Mol Genet</addtitle><date>2015-02-01</date><risdate>2015</risdate><volume>24</volume><issue>3</issue><spage>891</spage><epage>898</epage><pages>891-898</pages><issn>0964-6906</issn><eissn>1460-2083</eissn><abstract>Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.</abstract><cop>England</cop><pmid>25256355</pmid><doi>10.1093/hmg/ddu480</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0964-6906 |
| ispartof | Human molecular genetics, 2015-02, Vol.24 (3), p.891-898 |
| issn | 0964-6906 1460-2083 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1652377012 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Asian Continental Ancestry Group - genetics Genes, MHC Class II Genetic Association Studies Genetic Predisposition to Disease Genetic Variation HLA-DP beta-Chains - genetics HLA-DQ beta-Chains - genetics Humans Japan Narcolepsy - genetics |
| title | New susceptibility variants to narcolepsy identified in HLA class II region |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-07T21%3A32%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=New%20susceptibility%20variants%20to%20narcolepsy%20identified%20in%20HLA%20class%20II%20region&rft.jtitle=Human%20molecular%20genetics&rft.au=Miyagawa,%20Taku&rft.date=2015-02-01&rft.volume=24&rft.issue=3&rft.spage=891&rft.epage=898&rft.pages=891-898&rft.issn=0964-6906&rft.eissn=1460-2083&rft_id=info:doi/10.1093/hmg/ddu480&rft_dat=%3Cproquest_cross%3E1652377012%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1652377012&rft_id=info:pmid/25256355&rfr_iscdi=true |