{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T23:37:36Z","timestamp":1777937856777,"version":"3.51.4"},"reference-count":16,"publisher":"SAGE Publications","issue":"10","license":[{"start":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T00:00:00Z","timestamp":1741996800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI169070"],"award-info":[{"award-number":["R01AI169070"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>The complement system has been suspected to play a role in multiple sclerosis (MS) due to presence of complement activation products in MS lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We sought to understand whether variation in the complement component 4 (C4) gene is associated with MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Here we used next-generation sequencing and our novel bioinformatics tool,\n                      <jats:italic>C4Investigator<\/jats:italic>\n                      , to interrogate C4 copy number variation in MS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      We found higher overall copy number of C4 in controls (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 10\n                      <jats:sup>\u221216<\/jats:sup>\n                      , odds ratio (OR) = 0.43, 95% confidence interval (CI): 0.37\u20130.49) compared to MS patients with European ancestry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>This finding suggests that lower C4 copies confer risk for MS, similar to associations seen in other autoimmune disorders.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585251324850","type":"journal-article","created":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T05:20:52Z","timestamp":1742016052000},"page":"1243-1246","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Copy number variation at the complement C4 locus is associated with risk for multiple sclerosis"],"prefix":"10.1177","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-5672","authenticated-orcid":false,"given":"Jacqueline","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wesley M","family":"Marin","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen J","family":"Wade","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rayo","family":"Suseno","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry","family":"Kizer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacy","family":"Caillier","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danillo G","family":"Augusto","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Biological Sciences, The University of North Carolina at Charlotte, Charlotte, NC, USA"},{"name":"Programa de P\u00f3s-Gradua\u00e7\u00e3o em Gen\u00e9tica, Universidade Federal do Paran\u00e1, Curitiba, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul J","family":"Norman","sequence":"additional","affiliation":[{"name":"Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO, USA"},{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6572-7962","authenticated-orcid":false,"given":"Jill A","family":"Hollenbach","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,3,15]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2009.04633.x"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2022.102979"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.5.2734"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/518257"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04332-3"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2015.06.010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(80)90042-8"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2008.03830.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24747"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1821778116"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30470-2"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav7188"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1101\/gr.213538.116"},{"key":"e_1_3_3_15_2","article-title":"High-throughput complement component 4 genomic sequence analysis with C4Investigator","volume":"103","author":"Marin WM","year":"2023","unstructured":"Marin WM, Augusto DG, Wade KJ, et al. High-throughput complement component 4 genomic sequence analysis with C4Investigator. 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