Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects

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Title Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects
Author Lill, Christina M; Liu, Tian; Schjeide, Brit-Maren M; Roehr, Johannes T; Akkad, Dennis A; Damotte, Vincent; Alcina, Antonio; Ortiz, Miguel A; Arroyo, Rafa; Lapuente, Aitzkoa Lopez de; Blaschke, Paul; Winkelmann, Alexander; Gerdes, Lisa-Ann; Luessi, Felix; Fernandez, Oscar; Izquierdo, Guillermo; Antiguedad, Alfredo; Hoffjan, Sabine; Cournu-Rebeix, Isabelle; Gromöller, Silvana; Faber, Hans; Liebsch, Maria; Meissner, Esther; Chanvillard, Coralie; Touze, Emmanuel; Pico, Fernando; Corcia, Philippe; Bahlo, Melanie; Booth, David R; Broadley, Simon; Brown, Matthew A; Browning, Brian L; Browning, Sharon R; Butzkueven, Helmut; Carroll, William M; Cox, Mathew B; Chapman, Caron; Clarke, Glynnis; Danoy, Patrick; Drysdale, Karen; Field, Judith; Foote, Simon J; Greer, Judith M; Griffiths, Lyn; Hadler, Johanna; Jensen, Cathy J; Johnson, Laura J; Kermode, Allan G; Heard, Robert N; Kilpatrick, Trevor J; Scott, Jeanette Lechner-; Marriott, Mark; Mason, Deborah; Moscato, Pablo; Pender, Michael P; Perreau, Victoria M; Rubio, Justin P; Scott, Rodney J; Slee, Mark; Stankovich, Jim; Stewart, Graeme J; Tajouri, Lotfi; Taylor, Bruce V; Wiley, James; Wilkins, Ella J; Dörner, Thomas; Steinhagen-Thiessen, Elisabeth; Baeckman, Lars; Heekeren, Hauke R; Li, Shu-Chen; Lindenberger, Ulman; Chan, Andrew; Hartung, Hans- Peter; Aktas, Orhan; Lohse, Peter; Kümpfel, Tania; Kubisch, Christian; Epplen, Joerg T; Zettl, Uwe K; Fontaine, Bertrand; Vandenbroeck, Koen; Matesanz, Fuencisla; Urcelay, Elena; Bertram, Lars; Zipp, Frauke
Journal Name Journal of Medical Genetics
Year Published 2012
Place of publication United Kingdom
Publisher BMJ Publishing Group
Abstract Background: Single nucleotide polymorphisms (SNPs) rs429358 (ε4) and rs7412 (ε2), both invoking changes in the amino-acid sequence of the apolipoprotein E (APOE) 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. Methods: We genotyped 12 740 subjects hitherto not studied for their APOE status, imputed raw genotype data from 8739 subjects from five independent genomewide association studies datasets using the most recent high-resolution reference panels, and extracted genotype data for 8265 subjects from previous candidate gene assessments. Results: 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 13 913 MS cases and 15 831 controls (OR=0.95, p=0.259, and OR 1.07, p=0.0569, for rs429358 and rs7412, respectively). Conclusion: Given the large sample size of our analyses, it is unlikely that the two APOE missense SNPs studied here exert any relevant effects on MS susceptibility.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1136/jmedgenet-2012-101175
Copyright Statement Copyright remains with the authors 2012. The attached file is reproduced here in accordance with the copyright policy of the publisher. For information about this journal please refer to the journal’s website or contact the authors.
Volume 49
Issue Number 9
Page from 558
Page to 562
ISSN 1468-6244
Date Accessioned 2012-10-23
Date Available 2013-06-18T00:03:55Z
Language en_US
Research Centre Griffith Health Institute; Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Central Nervous System
URI http://hdl.handle.net/10072/47633
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1

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