Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects. Issue 9 (11th September 2012)

• Record Type: Journal Article
• Authors: Lill, Christina M; Liu, Tian; Schjeide, Brit-Maren M; Roehr, Johannes T; Akkad, Denis A; Damotte, Vincent; Alcina, Antonio; Ortiz, Miguel A; Arroyo, Rafa; Lopez de Lapuente, Aitzkoa; Blaschke, Paul; Winkelmann, Alexander; Gerdes, Lisa-Ann; Luessi, Felix; Fernadez, Oscar; Izquierdo, Guillermo; Antigüedad, Alfredo; Hoffjan, Sabine; Cournu-Rebeix, Isabelle; Gromöller, Silvana; Faber, Hans; Liebsch, Maria; Meissner, Esther; Chanvillard, Coralie; Touze, Emmanuel; Pico, Fernando; Corcia, Philippe; 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;
• Other Names: contributor.
• Is Part Of: Journal of medical genetics. Volume 49:Issue 9(2012)
• Page Start: 558
• Page End: 562
• Publication Date: 2012-09-11
• Subjects: Multiple sclerosis -- APOE -- meta-analysis -- genome-wide association study -- imputation; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2012-101175
• Languages: English
• ISSNs: 1468-6244

Abstract

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 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.