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Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects
Citation
Lill, CM and Liu, T and Schjeide, B-MM and Roehr, JT and Akkad, DA and Damotte, V and Alcina, A and Ortiz, MA and Arroyo, R and de Lapuente, AL and Blaschke, P and Winkelmann, A and Gerdes, L-A and Luessi, F and Fernadez, O and Izquierdo, G and Antiguedad, A and Hoffjan, S and Cournu-Rebeix, I and Gromoller, S and Faber, H and Liebsch, M and Meissner, E and Chanvillard, C and Touze, E and Pico, F and Corcia, P and Bahlo, M and Booth, DR and Broadley, SA and Brown, MA and Browning, BL and Browning, SR and Butzkueven, H and Carroll, WM and Cox, MB and Chapman, C and Clarke, G and Danoy, P and Drysdale, K and Field, J and Foote, SJ and Greer, JM and Griffiths, LR and Hadler, J and Jensen, CJ and Johnson, LJ and Kermode, AG and Heard, RN and Kilpatrick, TJ and Lechner-Scott, J and Marriott, M and Mason, D and Moscato, P and Pender, MP and Perreau, VM and Rubio, JP and Scott, RJ and Slee, M and Stankovich, J and Stewart, GJ and Tajouri, L and Taylor, BV and Wiley, J and Wilkins, EJ and Dorner, T and Steinhagen-Thiessen, E and Baeckman, L and Heekeren, HR and Li, S-C and Lindenberger, U and Chan, A and Hartung, H-P and Aktas, O and Lohse, P and Kumpfel, T and Kubisch, C and Epplen, JT and Zettl, U and Fontaine, B and Vandenbroeck, K and Matesanz, F and Urcelay, E and Bertram, L and Zipp, F, Closing the case of APOE in multiple sclerosis: no association with disease risk in over 29 000 subjects, Journal of Medical Genetics, 49, (9) pp. 558-562. ISSN 0022-2593 (2012) [Refereed Article]
Copyright Statement
Copyright 2012 British Medical Journal Publishing Group
DOI: doi:10.1136/jmedgenet-2012-101175
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.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Research Division: | Medical and Health Sciences |
| Research Group: | Neurosciences |
| Research Field: | Central Nervous System |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Nervous System and Disorders |
| Author: | Drysdale, K (Ms Karen Drysdale) |
| Author: | Foote, SJ (Professor Simon Foote) |
| Author: | Taylor, BV (Professor Bruce Taylor) |
| ID Code: | 82604 |
| Year Published: | 2012 |
| Web of Science® Times Cited: | 16 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2013-02-07 |
| Last Modified: | 2017-11-07 |
| Downloads: | 0 |
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