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

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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., Liu, T., Schjeide, B.M., Roehr, J.T., Akkad, D.A., Damotte, V., Alcina, A., Ortiz, M.A., Arroyo, R., Lopez de Lapuente, A., Blaschke, P., Winkelmann, A., Gerdes, L.A., Luessi, F., Fernadez, O., Izquierdo, G., Antiguedad, A., Hoffjan, S., Cournu-Rebeix, I., Gromoeller, S., Faber, H., Liebsch, M., Meissner, E., Chanvillard, C., Touze, E., Pico, F., Corcia, P., Doerner, T., Steinhagen-Thiessen, E., Baeckman, L., Heekeren, H.R., Li, S.C., Lindenberger, U., Chan, A., Hartung, H.P., Aktas, O., Lohse, P., Kuempfel, T., Kubisch, C., Epplen, J.T., Zettl, U.K., Fontaine, B., Vandenbroeck, K., Matesanz, F., Urcelay, E., 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
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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