Type

Journal Article

Authors

Colin P Doherty
Norman Delanty
Sanjay M Sisodiya
David B Goldstein
Nicholas W Wood
Amre Shahwan
Gianpiero L Cavalleri
Peter Kinirons

Subjects

Biochemistry

Topics
genetic variation alleles receptors gaba a mutation genotype haplotypes genetics humans epilepsy classification gabrg2 protein human polymorphism single nucleotide

Examining the role of common genetic variation in the gamma2 subunit of the GABA(A) receptor in epilepsy using tagging SNPs. (2006)

Abstract Mutations in the gamma2 subunit gene of the GABA(A) receptor, GABRG2, have been shown to cause generalised epilepsy syndromes in rare familial cases. Here we set out to examine whether common variation in GABRG2 predisposes to the development of common, complex forms of epilepsy in two large independent cohorts. We have applied a tagging single nucleotide polymorphism (tSNP) technique allowing us to satisfactorily represent common variation in the gene. However, to ensure maximal representation of functional variation and in particular in cases of low minor allele frequency (MAF), we have identified and forced known functional variation as tagging SNPs. We examined the association between tagging SNPs and subtypes of epilepsy in two independent cohorts; the first consisted of 677 cases and 384 healthy controls, the second of 684 cases and 277 healthy controls. We failed to detect any variation that conferred an increased risk of disease development in both cohorts. Our results suggest that common variants of strong effect in GABRG2 do not appear to play a role in the development of common, complex forms of epilepsy. This report illustrates a number of important features of study design in genetic association studies, including the simultaneous use of map and sequence-based techniques and the necessity of replication before robust conclusions can be drawn from results.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Colin P Doherty, Norman Delanty, Sanjay M Sisodiya, David B Goldstein, Nicholas W Wood, Amre Shahwan, Gianpiero L Cavalleri, Peter Kinirons

Experts in our system

1
Colin P Doherty
Trinity College Dublin
Total Publications: 35
 
2
Norman Delanty
Royal College of Surgeons in Ireland
Total Publications: 41
 
3
Sanjay M Sisodiya
Royal College of Surgeons in Ireland
Total Publications: 13
 
4
David B Goldstein
Royal College of Surgeons in Ireland
 
5
Gianpiero L Cavalleri
Royal College of Surgeons in Ireland
Total Publications: 35