Closing the case of APOE in multiple sclerosis : no association with disease risk in over 29 000 subjects
(2012) In Journal of Medical Genetics 49(9). p.62-558- 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... (More)
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.
(Less)
- author
- author collaboration
- publishing date
- 2012-09
- type
- Contribution to journal
- publication status
- published
- keywords
- Apolipoproteins E/genetics, Databases, Genetic, European Continental Ancestry Group/genetics, Genetic Association Studies, Genetic Predisposition to Disease, Humans, Multiple Sclerosis/genetics, Polymorphism, Single Nucleotide/genetics, Risk Factors
- in
- Journal of Medical Genetics
- volume
- 49
- issue
- 9
- pages
- 62 - 558
- publisher
- BMJ Publishing Group
- external identifiers
-
- pmid:22972946
- scopus:84870262595
- ISSN
- 0022-2593
- DOI
- 10.1136/jmedgenet-2012-101175
- language
- English
- LU publication?
- no
- id
- 939093a7-a166-4828-8040-e3221c771aca
- date added to LUP
- 2021-01-17 18:59:09
- date last changed
- 2024-01-03 04:54:53
@article{939093a7-a166-4828-8040-e3221c771aca,
abstract = {{<p>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.</p><p>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.</p><p>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).</p><p>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.</p>}},
author = {{Lill, Christina M and Liu, Tian and Schjeide, Brit-Maren M and Roehr, Johannes T and Akkad, Denis A and Damotte, Vincent and Alcina, Antonio and Ortiz, Miguel A and Arroyo, Rafa and Lopez de Lapuente, Aitzkoa and Blaschke, Paul and Winkelmann, Alexander and Gerdes, Lisa-Ann and Luessi, Felix and Fernadez, Oscar and Izquierdo, Guillermo and Antigüedad, Alfredo and Hoffjan, Sabine and Cournu-Rebeix, Isabelle and Gromöller, Silvana and Faber, Hans and Liebsch, Maria and Meissner, Esther and Chanvillard, Coralie and Touze, Emmanuel and Pico, Fernando and Corcia, Philippe and Dörner, Thomas and Steinhagen-Thiessen, Elisabeth and Baeckman, Lars and Heekeren, Hauke R and Li, Shu-Chen and Lindenberger, Ulman and Chan, Andrew and Hartung, Hans-Peter and Aktas, Orhan and Lohse, Peter and Kümpfel, Tania and Kubisch, Christian and Epplen, Joerg T and Zettl, Uwe K and Fontaine, Bertrand and Vandenbroeck, Koen and Matesanz, Fuencisla and Urcelay, Elena and Bertram, Lars and Zipp, Frauke}},
issn = {{0022-2593}},
keywords = {{Apolipoproteins E/genetics; Databases, Genetic; European Continental Ancestry Group/genetics; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Multiple Sclerosis/genetics; Polymorphism, Single Nucleotide/genetics; Risk Factors}},
language = {{eng}},
number = {{9}},
pages = {{62--558}},
publisher = {{BMJ Publishing Group}},
series = {{Journal of Medical Genetics}},
title = {{Closing the case of APOE in multiple sclerosis : no association with disease risk in over 29 000 subjects}},
url = {{http://dx.doi.org/10.1136/jmedgenet-2012-101175}},
doi = {{10.1136/jmedgenet-2012-101175}},
volume = {{49}},
year = {{2012}},
}