Closing the case of APOE in multiple sclerosis: No association with disease risk in over 29 000 subjects
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
- 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
Originalsprache | Englisch |
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Seiten (von - bis) | 558-562 |
Seitenumfang | 5 |
Fachzeitschrift | Journal of medical genetics |
Jahrgang | 49 |
Ausgabenummer | 9 |
Publikationsstatus | Veröffentlicht - 1 Sept. 2012 |
Peer-Review-Status | Ja |
Extern publiziert | Ja |
Externe IDs
PubMed | 22972946 |
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ORCID | /0000-0001-8409-5390/work/142254941 |