{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T12:40:06Z","timestamp":1773664806722,"version":"3.50.1"},"reference-count":11,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2012,7,23]]},"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Single nucleotide polymorphisms (SNPs) rs429358 (\u03b54) and rs7412 (\u03b52), both invoking changes in the amino-acid sequence of the apolipoprotein E (<jats:italic>APOE<\/jats:italic>) gene, have previously been tested for association with multiple sclerosis (MS) risk. However, none of these studies was sufficiently powered to detect modest effect sizes at acceptable type-I error rates. As both SNPs are only imperfectly captured on commonly used microarray genotyping platforms, their evaluation in the context of genome-wide association studies has been hindered until recently.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We genotyped 12\u2005740 subjects hitherto not studied for their <jats:italic>APOE<\/jats:italic> status, imputed raw genotype data from 8739 subjects from five independent genome-wide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Despite sufficient power to detect associations at genome-wide significance thresholds across a range of ORs, our analyses did not support a role of rs429358 or rs7412 on MS susceptibility. This included meta-analyses of the combined data across 13\u2005913 MS cases and 15\u2005831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Given the large sample size of our analyses, it is unlikely that the two <jats:italic>APOE<\/jats:italic> missense SNPs studied here exert any relevant effects on MS susceptibility.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jmedgenet-2012-101175","type":"journal-article","created":{"date-parts":[[2012,9,12]],"date-time":"2012-09-12T02:38:03Z","timestamp":1347417483000},"page":"558-562","source":"Crossref","is-referenced-by-count":29,"title":["Closing the case of <i>APOE<\/i> in multiple sclerosis: no association with disease risk in over 29\u2005000 subjects: Figure 1"],"prefix":"10.1136","volume":"49","author":[{"given":"Christina M","family":"Lill","sequence":"first","affiliation":[{"name":"1Deptartment of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany"},{"name":"2Deptartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Liu","sequence":"additional","affiliation":[{"name":"2Deptartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany"},{"name":"3Max Planck Institute for Human Development, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brit-Maren M","family":"Schjeide","sequence":"additional","affiliation":[{"name":"2Deptartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes T","family":"Roehr","sequence":"additional","affiliation":[{"name":"2Deptartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Denis A","family":"Akkad","sequence":"additional","affiliation":[{"name":"4Department of Human Genetics, Ruhr University, Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Damotte","sequence":"additional","affiliation":[{"name":"5INSERM-CNRS-UPMC-ICM, UMR 975-7225, Institut cerveau Moelle, Hopital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Alcina","sequence":"additional","affiliation":[{"name":"6Institution Parasitolog\u00eda y Biomedicina \u2018L\u00f3pez Neyra\u2019, CSIC, Granada, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miguel A","family":"Ortiz","sequence":"additional","affiliation":[{"name":"7Inmunolog\u00eda Department, Hospital Cl\u00ednico San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafa","family":"Arroyo","sequence":"additional","affiliation":[{"name":"8Multiple Sclerosis Unit, Neurology Department, Hospital Cl\u00ednico San Carlos, Instituto de Investigaci\u00f3n Sanitaria San Carlos (IdISSC), Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aitzkoa","family":"Lopez de Lapuente","sequence":"additional","affiliation":[{"name":"9Neurogenomiks Laboratory, Department of Neuroscience, University of the Basque Country UPV\/EHU, Leioa, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Blaschke","sequence":"additional","affiliation":[{"name":"10Department of Neurology, University of Rostock, Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Winkelmann","sequence":"additional","affiliation":[{"name":"10Department of Neurology, University of Rostock, Rostock, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa-Ann","family":"Gerdes","sequence":"additional","affiliation":[{"name":"11Institute for Clinical Neuroimmunology, Ludwig Maximilian University, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Luessi","sequence":"additional","affiliation":[{"name":"1Deptartment of Neurology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Fernadez","sequence":"additional","affiliation":[{"name":"12Unidad de Esclerosis M\u00faltiple, Hospital Virgen Macarena, Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guillermo","family":"Izquierdo","sequence":"additional","affiliation":[{"name":"12Unidad de Esclerosis M\u00faltiple, Hospital Virgen Macarena, Sevilla, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Antig\u00fcedad","sequence":"additional","affiliation":[{"name":"13Servicio de Neurolog\u00eda, Hospital de Basurto, Bilbao, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Hoffjan","sequence":"additional","affiliation":[{"name":"4Department of Human Genetics, Ruhr University, Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Cournu-Rebeix","sequence":"additional","affiliation":[{"name":"5INSERM-CNRS-UPMC-ICM, UMR 975-7225, Institut cerveau Moelle, Hopital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"14Department of Neurology, Hopital Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvana","family":"Grom\u00f6ller","sequence":"additional","affiliation":[{"name":"2Deptartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Faber","sequence":"additional","affiliation":[{"name":"15Section of Neurology, Max Planck Institute for Psychiatry, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Liebsch","sequence":"additional","affiliation":[{"name":"2Deptartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Meissner","sequence":"additional","affiliation":[{"name":"2Deptartment of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coralie","family":"Chanvillard","sequence":"additional","affiliation":[{"name":"16Experimental and Clinical Research Center, a joint cooperation between the Charit\u00e9 Medical Faculty and the Max-Delbr\u00fcck Center for Molecular Medicine, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuel","family":"Touze","sequence":"additional","affiliation":[{"name":"17Department of Neurology, H\u00f4pital Sainte-Anne, Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Pico","sequence":"additional","affiliation":[{"name":"18Department of Neurology, Centre Hospitalier de Versailles, Le Chesnay, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Corcia","sequence":"additional","affiliation":[{"name":"19Department of Neurology, Centre Hospitalier Regional Universitaire, Tours, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"D\u00f6rner","sequence":"additional","affiliation":[{"name":"20Department of Medicine, Rheumatology, and Clinical Immunology, Charit\u00e9 University Medicine, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Steinhagen-Thiessen","sequence":"additional","affiliation":[{"name":"21Interdisciplinary Metabolic Center, Lipids Clinic, Charit\u00e9 University Medicine, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Baeckman","sequence":"additional","affiliation":[{"name":"22Aging Research Center, Karolinska Institute, Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hauke R","family":"Heekeren","sequence":"additional","affiliation":[{"name":"3Max Planck Institute for Human Development, Berlin, Germany"},{"name":"23Department of Education and Psychology, Free University, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu-Chen","family":"Li","sequence":"additional","affiliation":[{"name":"3Max Planck Institute for Human Development, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulman","family":"Lindenberger","sequence":"additional","affiliation":[{"name":"3Max Planck Institute for Human Development, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Chan","sequence":"additional","affiliation":[{"name":"24Department of Neurology, Ruhr University, Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[{"name":"25Department of Neurology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Orhan","family":"Aktas","sequence":"additional","affiliation":[{"name":"25Department of Neurology, Medical Faculty, Heinrich Heine University, D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Lohse","sequence":"additional","affiliation":[{"name":"26Department of Clinical Chemistry, Ludwig Maximilian University, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tania","family":"K\u00fcmpfel","sequence":"additional","affiliation":[{"name":"11Institute for Clinical Neuroimmunology, Ludwig Maximilian University, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Kubisch","sequence":"additional","affiliation":[{"name":"27Institute of Human Genetics, University of Ulm, Ulm, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joerg T","family":"Epplen","sequence":"additional","affiliation":[{"name":"4Department of Human Genetics, Ruhr University, Bochum, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uwe 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