The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study
In the recently published meta-analysis of multiple sclerosis genome-wide association studies De Jager et al. identified three single nucleotide polymorphisms associated to MS: rs17824933 (CD6), rs1800693 (TNFRSF1A) and rs17445836 (61.5 kb from IRF8). To refine our understanding of these association...
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| description | In the recently published meta-analysis of multiple sclerosis genome-wide association studies De Jager et al. identified three single nucleotide polymorphisms associated to MS: rs17824933 (CD6), rs1800693 (TNFRSF1A) and rs17445836 (61.5 kb from IRF8). To refine our understanding of these associations we sought to replicate these findings in a large more extensive independent sample set of 11 populations of European origin.
We calculated individual and combined associations using a meta-analysis method by Kazeem and Farral (2005). We confirmed the association of rs1800693 in TNFRSF1A (p 4.19 × 10-7, OR 1.12, 7,665 cases, 8,051 controls) and rs17445836 near IRF8 (p 5.35 × 10-10, OR 0.84, 6,895 cases, 7,580 controls and 596 case-parent trios) The SNP rs17824933 in CD6 also showed nominally significant evidence for association (p 2.19 × 10-5, OR 1.11, 8,047 cases, 9,174 controls, 604 case-parent trios).
Variants in TNFRSF1A and in the vicinity of IRF8 were confirmed to be associated in these independent cohorts, which supports the role of these loci in etiology of multiple sclerosis. The variant in CD6 reached genome-wide significance after combining the data with the original meta-analysis. Fine mapping is required to identify the predisposing variants in the loci and future functional studies will refine their molecular role in MS pathogenesis. |
| doi_str_mv | 10.1371/journal.pone.0018813 |
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We calculated individual and combined associations using a meta-analysis method by Kazeem and Farral (2005). We confirmed the association of rs1800693 in TNFRSF1A (p 4.19 × 10-7, OR 1.12, 7,665 cases, 8,051 controls) and rs17445836 near IRF8 (p 5.35 × 10-10, OR 0.84, 6,895 cases, 7,580 controls and 596 case-parent trios) The SNP rs17824933 in CD6 also showed nominally significant evidence for association (p 2.19 × 10-5, OR 1.11, 8,047 cases, 9,174 controls, 604 case-parent trios).
Variants in TNFRSF1A and in the vicinity of IRF8 were confirmed to be associated in these independent cohorts, which supports the role of these loci in etiology of multiple sclerosis. The variant in CD6 reached genome-wide significance after combining the data with the original meta-analysis. Fine mapping is required to identify the predisposing variants in the loci and future functional studies will refine their molecular role in MS pathogenesis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0018813</identifier><identifier>PMID: 21552549</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Antigens, CD - genetics ; Antigens, Differentiation, T-Lymphocyte - genetics ; Apoptosis ; Biology ; Case-Control Studies ; CD6 antigen ; Cell adhesion & migration ; Chromosomes ; Consortia ; Development and progression ; Etiology ; Gene mapping ; Genetic aspects ; Genetic research ; Genome-wide association studies ; Genomes ; Genomics ; Humans ; Independent sample ; Interferon Regulatory Factors - genetics ; Leukemia ; Loci ; Medicin och hälsovetenskap ; Medicine ; Meta-analysis ; Multiple sclerosis ; Multiple Sclerosis - genetics ; Mutation ; Pathogenesis ; Polymorphism, Single Nucleotide - genetics ; Ratios ; Receptors, Tumor Necrosis Factor, Type I - genetics ; Single nucleotide polymorphisms ; Single-nucleotide polymorphism ; Tumor necrosis factor-TNF</subject><ispartof>PloS one, 2011-04, Vol.6 (4), p.e18813-e18813</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011 Leppä et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Leppä et al. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c915t-cf4bc7da6f610689176e5447db48a8420dce81dce8ca967751a43fbc6b1942313</citedby><cites>FETCH-LOGICAL-c915t-cf4bc7da6f610689176e5447db48a8420dce81dce8ca967751a43fbc6b1942313</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084233/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084233/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,554,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21552549$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:122490005$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><contributor>Chatenoud, Lucienne</contributor><creatorcontrib>International, Multiple Sclerosis Genetics Consortium</creatorcontrib><creatorcontrib>International Multiple Sclerosis Genetics Consortium</creatorcontrib><creatorcontrib>The International Multiple Sclerosis Genetics Consortium</creatorcontrib><title>The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>In the recently published meta-analysis of multiple sclerosis genome-wide association studies De Jager et al. identified three single nucleotide polymorphisms associated to MS: rs17824933 (CD6), rs1800693 (TNFRSF1A) and rs17445836 (61.5 kb from IRF8). To refine our understanding of these associations we sought to replicate these findings in a large more extensive independent sample set of 11 populations of European origin.
We calculated individual and combined associations using a meta-analysis method by Kazeem and Farral (2005). We confirmed the association of rs1800693 in TNFRSF1A (p 4.19 × 10-7, OR 1.12, 7,665 cases, 8,051 controls) and rs17445836 near IRF8 (p 5.35 × 10-10, OR 0.84, 6,895 cases, 7,580 controls and 596 case-parent trios) The SNP rs17824933 in CD6 also showed nominally significant evidence for association (p 2.19 × 10-5, OR 1.11, 8,047 cases, 9,174 controls, 604 case-parent trios).
Variants in TNFRSF1A and in the vicinity of IRF8 were confirmed to be associated in these independent cohorts, which supports the role of these loci in etiology of multiple sclerosis. The variant in CD6 reached genome-wide significance after combining the data with the original meta-analysis. Fine mapping is required to identify the predisposing variants in the loci and future functional studies will refine their molecular role in MS pathogenesis.</description><subject>Analysis</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, Differentiation, T-Lymphocyte - genetics</subject><subject>Apoptosis</subject><subject>Biology</subject><subject>Case-Control Studies</subject><subject>CD6 antigen</subject><subject>Cell adhesion & migration</subject><subject>Chromosomes</subject><subject>Consortia</subject><subject>Development and progression</subject><subject>Etiology</subject><subject>Gene mapping</subject><subject>Genetic aspects</subject><subject>Genetic research</subject><subject>Genome-wide association studies</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Humans</subject><subject>Independent sample</subject><subject>Interferon Regulatory Factors - genetics</subject><subject>Leukemia</subject><subject>Loci</subject><subject>Medicin och hälsovetenskap</subject><subject>Medicine</subject><subject>Meta-analysis</subject><subject>Multiple sclerosis</subject><subject>Multiple Sclerosis - genetics</subject><subject>Mutation</subject><subject>Pathogenesis</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Ratios</subject><subject>Receptors, Tumor Necrosis Factor, Type I - genetics</subject><subject>Single nucleotide polymorphisms</subject><subject>Single-nucleotide polymorphism</subject><subject>Tumor necrosis factor-TNF</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><sourceid>DOA</sourceid><recordid>eNqNk-Fr1DAYxosobp7-B6KBgSJ4Z9KkaesHYUxPD4aDbfo1vE3f3mXmmrNpp_vvTb3evMoEKbTh7e95Qp68bxQ9ZXTGeMreXLmuqcHONq7GGaUsyxi_Fx2ynMdTGVN-f299ED3y_orShGdSPowOYpYkcSLyw6i7XCFZYo2t0QS8d9pAa1xNXEWuoTFQt56Ympy8l6_J5ef5-cWcHROoS7I4n2ekdWTd2dZsLBKvLTbOG_-WwLaqsW6xIRo8TrWr28ZZ4tuuvHkcPajAenwyfCfRl_mHy5NP09Ozj4uT49OpzlnSTnUlCp2WICvJqMxylkpMhEjLQmSQiZiWGjPWvzTkMk0TBoJXhZYFy0XMGZ9Ez7e-G-u8GhLzisV5GhzjwEyixZYoHVypTWPW0NwoB0b9LrhmqaAJJ7GoWFnxiiZMcy0EZlhAUkrBgGooecUgeE23Xv4Hbrpi5DaUvoUVqnAGkcjA5__kN40r_4h2QhbHIqf9PU6id8PJumKNZZ90A3ZsMfpTm5VaumvFaQiO82DwcjBo3PcOfavWxmu0Fmp0nVdZylPKU5kF8ugv8u4gB2oJIStTVy5sq3tPdSyCTR5LQQM1u4MKT4lrE1oEKxPqI8GrkaBvI_zZLqHzXi0uzv-fPfs6Zl_ssSsE2668s13f-34Mii2oQ2_7BqvbjBlV_SDu0lD9IKphEIPs2f793Ip2k8d_AQ2CLp8</recordid><startdate>20110428</startdate><enddate>20110428</enddate><creator>International, Multiple Sclerosis Genetics Consortium</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><scope>DOA</scope></search><sort><creationdate>20110428</creationdate><title>The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study</title><author>International, Multiple Sclerosis Genetics Consortium</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c915t-cf4bc7da6f610689176e5447db48a8420dce81dce8ca967751a43fbc6b1942313</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Analysis</topic><topic>Antigens, CD - 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genetics</topic><topic>Single nucleotide polymorphisms</topic><topic>Single-nucleotide polymorphism</topic><topic>Tumor necrosis factor-TNF</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>International, Multiple Sclerosis Genetics Consortium</creatorcontrib><creatorcontrib>International Multiple Sclerosis Genetics Consortium</creatorcontrib><creatorcontrib>The International Multiple Sclerosis Genetics Consortium</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection (ProQuest)</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>International, Multiple Sclerosis Genetics Consortium</au><au>Chatenoud, Lucienne</au><aucorp>International Multiple Sclerosis Genetics Consortium</aucorp><aucorp>The International Multiple Sclerosis Genetics Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-04-28</date><risdate>2011</risdate><volume>6</volume><issue>4</issue><spage>e18813</spage><epage>e18813</epage><pages>e18813-e18813</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>In the recently published meta-analysis of multiple sclerosis genome-wide association studies De Jager et al. identified three single nucleotide polymorphisms associated to MS: rs17824933 (CD6), rs1800693 (TNFRSF1A) and rs17445836 (61.5 kb from IRF8). To refine our understanding of these associations we sought to replicate these findings in a large more extensive independent sample set of 11 populations of European origin.
We calculated individual and combined associations using a meta-analysis method by Kazeem and Farral (2005). We confirmed the association of rs1800693 in TNFRSF1A (p 4.19 × 10-7, OR 1.12, 7,665 cases, 8,051 controls) and rs17445836 near IRF8 (p 5.35 × 10-10, OR 0.84, 6,895 cases, 7,580 controls and 596 case-parent trios) The SNP rs17824933 in CD6 also showed nominally significant evidence for association (p 2.19 × 10-5, OR 1.11, 8,047 cases, 9,174 controls, 604 case-parent trios).
Variants in TNFRSF1A and in the vicinity of IRF8 were confirmed to be associated in these independent cohorts, which supports the role of these loci in etiology of multiple sclerosis. The variant in CD6 reached genome-wide significance after combining the data with the original meta-analysis. Fine mapping is required to identify the predisposing variants in the loci and future functional studies will refine their molecular role in MS pathogenesis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21552549</pmid><doi>10.1371/journal.pone.0018813</doi><tpages>e18813</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; SWEPUB Freely available online; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Antigens, CD - genetics Antigens, Differentiation, T-Lymphocyte - genetics Apoptosis Biology Case-Control Studies CD6 antigen Cell adhesion & migration Chromosomes Consortia Development and progression Etiology Gene mapping Genetic aspects Genetic research Genome-wide association studies Genomes Genomics Humans Independent sample Interferon Regulatory Factors - genetics Leukemia Loci Medicin och hälsovetenskap Medicine Meta-analysis Multiple sclerosis Multiple Sclerosis - genetics Mutation Pathogenesis Polymorphism, Single Nucleotide - genetics Ratios Receptors, Tumor Necrosis Factor, Type I - genetics Single nucleotide polymorphisms Single-nucleotide polymorphism Tumor necrosis factor-TNF |
| title | The genetic association of variants in CD6, TNFRSF1A and IRF8 to multiple sclerosis: a multicenter case-control study |
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