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

Lill, C. M., Liu, T., Schjeide, B. M., Roehr, J. T., Akkad, D. A., Damotte, V., et al. (2012). Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects. Journal of Medical Genetics (London), 49(9), 558-562. doi:DOI 10.1136/jmedgenet-2012-101175.

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 Creators:
Lill, C. M.1, Author           
Liu, T., Author
Schjeide, B. M.1, Author           
Roehr, J. T., Author
Akkad, D. A., Author
Damotte, V., Author
Alcina, A., Author
Ortiz, M. A., Author
Arroyo, R., Author
de Lapuente, A. L., Author
Blaschke, P., Author
Winkelmann, A., Author
Gerdes, L. A., Author
Luessi, F., Author
Fernadez, O., Author
Izquierdo, G., Author
Antiguedad, A., Author
Hoffjan, S., Author
Cournu-Rebeix, I., Author
Gromöller, S., Author
Faber, H., AuthorLiebsch, M.1, Author           Meissner, E.1, Author           Chanvillard, C., AuthorTouze, E., AuthorPico, F., AuthorCorcia, P., AuthorDörner, T., AuthorSteinhagen-Thiessen, E., AuthorBaeckman, L., AuthorHeekeren, H. R., AuthorLi, S. C., AuthorLindenberger, U., AuthorChan, A., AuthorHartung, H. P., AuthorAktas, O., AuthorLohse, P., AuthorKumpfel, T., AuthorKubisch, C., AuthorEpplen, J. T., AuthorZettl, U. K., AuthorFontaine, B., AuthorVandenbroeck, K., AuthorMatesanz, F., AuthorUrcelay, E., AuthorBertram, L.1, Author           Zipp, F., Author more..
Affiliations:
1Neuropsychiatric Genetics (Lars Bertram), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, Berlin, Germany, ou_1479655              

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Free keywords: susceptibility metaanalysis severity
 Abstract: Background Single nucleotide polymorphisms (SNPs) rs429358 (epsilon 4) and rs7412 (epsilon 2), 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.

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Language(s): eng - English
 Dates: 2012-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: DOI 10.1136/jmedgenet-2012-101175
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Title: Journal of Medical Genetics (London)
  Other : J Med Genet
Source Genre: Journal
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Publ. Info: London : British Medical Association
Pages: - Volume / Issue: 49 (9) Sequence Number: - Start / End Page: 558 - 562 Identifier: ISSN: 0022-2593
CoNE: https://pure.mpg.de/cone/journals/resource/954925415940