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

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Australia and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) - , Walter and Eliza Hall Institute of Medical Research (WEHI) (Autor:in)
  • Shu Chen Li - , Max Planck Institute for Human Development (Autor:in)
  • Johannes Gutenberg-Universität Mainz
  • Max Planck Institut für Molekulare Genetik
  • Ruhr-Universität Bochum
  • Sorbonne Université
  • Consejo Superior de Investigaciones Científicas (CSIC)
  • Complutense University
  • University of the Basque Country
  • Universität Rostock
  • Ludwig-Maximilians-Universität München (LMU)
  • Hospital Universitario Virgen Macarena
  • Hospital de Basurto
  • Max Planck Institute of Psychiatry
  • Max-Delbrück-Centrum für Molekulare Medizin (MDC)
  • GHU Paris Psychiatrie & Neuro sciences
  • Centre Hospitalier de Versailles
  • Université de Tours
  • Charité – Universitätsmedizin Berlin
  • Karolinska Institutet
  • Freie Universität (FU) Berlin
  • Heinrich Heine Universität Düsseldorf
  • Universität Ulm
  • Ikerbasque Basque Foundation for Science
  • Westmead Millennium Institute for Medical Research
  • Griffith University Queensland
  • Gold Coast University Hospital

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.

Details

OriginalspracheEnglisch
Seiten (von - bis)558-562
Seitenumfang5
FachzeitschriftJournal of medical genetics
Jahrgang49
Ausgabenummer9
PublikationsstatusVeröffentlicht - 1 Sept. 2012
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed 22972946
ORCID /0000-0001-8409-5390/work/142254941

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