Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies

Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample siz...

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Bibliographic Details
Published in:Lancet neurology 2014-09, Vol.13 (9), p.893-903
Main Author: Anon
Format: Article
Language:English
Subjects:
African Americans
Brain research
Collaboration
Epilepsy
Epilepsy - genetics
Genes
Genome-Wide Association Study - statistics & numerical data
Genomes
Humans
Meta-analysis
Neurology
Quality control
Regression analysis
Studies
Systematic review
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Summary:Summary Background The epilepsies are a clinically heterogeneous group of neurological disorders. Despite strong evidence for heritability, genome-wide association studies have had little success in identification of risk loci associated with epilepsy, probably because of relatively small sample sizes and insufficient power. We aimed to identify risk loci through meta-analyses of genome-wide association studies for all epilepsy and the two largest clinical subtypes (genetic generalised epilepsy and focal epilepsy). Methods We combined genome-wide association data from 12 cohorts of individuals with epilepsy and controls from population-based datasets. Controls were ethnically matched with cases. We phenotyped individuals with epilepsy into categories of genetic generalised epilepsy, focal epilepsy, or unclassified epilepsy. After standardised filtering for quality control and imputation to account for different genotyping platforms across sites, investigators at each site conducted a linear mixed-model association analysis for each dataset. Combining summary statistics, we conducted fixed-effects meta-analyses of all epilepsy, focal epilepsy, and genetic generalised epilepsy. We set the genome-wide significance threshold at p
ISSN:1474-4422
1474-4465
DOI:10.1016/S1474-4422(14)70171-1