Imperial College London


Faculty of MedicineDepartment of Brain Sciences

Professor of Neurology and Genomic Medicine



m.johnson Website




E419Burlington DanesHammersmith Campus






BibTex format

author = {International, League Against Epilepsy Consortium on Complex Epilepsies},
doi = {10.1016/S1474-4422(14)70171-1},
journal = {Lancet Neurology},
pages = {893--903},
title = {Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies},
url = {},
volume = {13},
year = {2014}

RIS format (EndNote, RefMan)

AB - 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<1·66×10(-8). FINDINGS: We included 8696 cases and 26157 controls in our analysis. Meta-analysis of the all-epilepsy cohort identified loci at 2q24.3 (p=8·71×10(-10)), implicating SCN1A, and at 4p15.1 (p=5·44×10(-9)), harbouring PCDH7, which encodes a protocadherin molecule not previously implicated in epilepsy. For the cohort of genetic generalised epilepsy, we noted a single signal at 2p16.1 (p=9·99×10(-9)), implicating VRK2 or FANCL. No single nucleotide polymorphism achieved genome-wide significance for focal epilepsy. INTERPRETATION: This meta-analysis describes a new locus not previously implicated in epilepsy and provides further evidence about the genetic architecture of these dis
AU - International,League Against Epilepsy Consortium on Complex Epilepsies
DO - 10.1016/S1474-4422(14)70171-1
EP - 903
PY - 2014///
SN - 1474-4465
SP - 893
TI - Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies
T2 - Lancet Neurology
UR -
UR -
VL - 13
ER -