Loading...
You are here:  Home  >  Advertisements  >  Current Article

Identifying Epilepsy Subtypes Based on Genetics

By   /  September 6, 2014  /  Comments Off on Identifying Epilepsy Subtypes Based on Genetics

    Print       Email
The Lancet Neurology
03 September 2014
Gt12_284-DNA

Researchers analyse genetic data to find loci linked to increased risks of different types of epilepsy

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).

Get The Full Articles at UNIVADIS (www.univadis.co.id)

http://www.univadis.co.id/just-published/Identifying-epilepsy-subtypes-based-on-genetics

    Print       Email
  • Published: 3 years ago on September 6, 2014
  • By:
  • Last Modified: September 6, 2014 @ 9:26 am
  • Filed Under: Advertisements

You might also like...

Apa dan Mengapa Univadis?

Read More →