title: Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience, [corrected] University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
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authors.lastname: Lindenberger
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authors.lastname: Fontaine
authors.forename: Koen
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authors.lastname: Vandenbroeck
authors.forename: Fuencisla
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authors.lastname: Matesanz
authors.forename: Elena
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mesh_terms: D001057:Apolipoproteins E / Q000235:genetics*; D030541:Databases, Genetic; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D001057:Apolipoproteins E