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 26 157 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 disorders, with the ultimate aim of assisting in disease 
classification and prognosis. The data suggest that specific loci can act 
pleiotropically raising risk for epilepsy broadly, or can have effects limited 
to a specific epilepsy subtype. Future genetic analyses might benefit from both 
lumping (ie, grouping of epilepsy types together) or splitting (ie, analysis of 
specific clinical subtypes).
FUNDING: International League Against Epilepsy and multiple governmental and 
philanthropic agencies.