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

Item Type:Article
Title:Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects
Creators Name:Lill, C.M. and Liu, T. and Schjeide, B.M. and Roehr, J.T. and Akkad, D.A. and Damotte, V. and Alcina, A. and Ortiz, M.A. and Arroyo, R. and Lopez de Lapuente, A. and Blaschke, P. and Winkelmann, A. and Gerdes, L.A. and Luessi, F. and Fernadez, O. and Izquierdo, G. and Antiguedad, A. and Hoffjan, S. and Cournu-Rebeix, I. and Gromoeller, S. and Faber, H. and Liebsch, M. and Meissner, E. and Chanvillard, C. and Touze, E. and Pico, F. and Corcia, P. and Doerner, T. and Steinhagen-Thiessen, E. and Baeckman, L. and Heekeren, H.R. and Li, S.C. and Lindenberger, U. and Chan, A. and Hartung, H.P. and Aktas, O. and Lohse, P. and Kuempfel, T. and Kubisch, C. and Epplen, J.T. and Zettl, U.K. and Fontaine, B. and Vandenbroeck, K. and Matesanz, F. and Urcelay, E. and Bertram, L. and Zipp, F.
Abstract:BACKGROUND: Single nucleotide polymorphisms (SNPs) rs429358 (epsilon4) and rs7412 (epsilon2), 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 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. 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.
Keywords:Apolipoproteins E, Genetic Databases, European Continental Ancestry Group, Genetic Association Studies, Genetic Predisposition to Disease, Multiple Sclerosis, Risk Factors, Single Nucleotide Polymorphism
Source:Journal of Medical Genetics
ISSN:0022-2593
Publisher:BMJ Publishing Group (U.K.)
Volume:49
Number:9
Page Range:558-562
Date:September 2012
Official Publication:https://doi.org/10.1136/jmedgenet-2012-101175
PubMed:View item in PubMed

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