dc.contributor.author | DOHERTY, COLIN | en |
dc.date.accessioned | 2015-05-19T14:57:21Z | |
dc.date.available | 2015-05-19T14:57:21Z | |
dc.date.issued | 2010 | en |
dc.date.submitted | 2010 | en |
dc.identifier.citation | Kasperavi-iüte, D. Catarino, C.B. Heinzen, E.L. Depondt, C. Cavalleri, G.L. Caboclo, L.O. Tate, S.K. Jamnadas-Khoda, J. Chinthapalli, K. Clayton, L.M.S. Shianna, K.V. Radtke, R.A. Mikati, M.A. Gallentine, W.B. Husain, A.M. Alhusaini, S. Leppert, D. Middleton, L.T. Gibson, R.A. Johnson, M.R. Matthews, P.M. Hosford, D. Heuser, K. Amos, L. Ortega, M. Zumsteg, D. Wieser, H.-G. Steinhoff, B.J. Krämer, G. Hansen, J. Dorn, T. Kantanen, A.-M. Gjerstad, L. Peuralinna, T. Hernandez, D.G. Eriksson, K.J. Kälviäinen, R.K. Doherty, C.P. Wood, N.W. Pandolfo, M. Duncan, J.S. Sander, J.W. Delanty, N. Goldstein, D.B. Sisodiya, S.M., Common genetic variation and susceptibility to partial epilepsies: A genome-wide association study, Brain, 133, 7, 2010, 2136 - 2147 | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/73954 | |
dc.description | PUBLISHED | en |
dc.description.abstract | Partial epilepsies have a substantial heritability. However, the actual genetic causes are largely unknown. In contrast to many
other common diseases for which genetic association-studies have successfully revealed common variants associated with
disease risk, the role of common variation in partial epilepsies has not yet been explored in a well-powered study. We under-
took a genome-wide association-study to identify common variants which influence risk for epilepsy shared amongst partial
epilepsy syndromes, in 3445 patients and 6935 controls of European ancestry. We did not identify any genome-wide significant
association. A few single nucleotide polymorphisms may warrant further investigation. We exclude common genetic variants
with effect sizes above a modest 1.3 odds ratio for a single variant as contributors to genetic susceptibility shared across the
partial epilepsies. We show that, at best, common genetic variation can only have a modest role in predisposition to the partial
epilepsies when considered across syndromes in Europeans. The genetic architecture of the partial epilepsies is likely to be very
complex, reflecting genotypic and phenotypic heterogeneity. Larger meta-analyses are required to identify variants of smaller
effect sizes (odds ratio
5
1.3) or syndrome-specific variants. Further, our results suggest research efforts should also be directed
towards identifying the multiple rare variants likely to account for at least part of the heritability of the partial epilepsies. Data
emerging from genome-wide association-studies will be valuable during the next serious challenge of interpreting all the
genetic variation emerging from whole-genome sequencing studies | en |
dc.description.sponsorship | This work was supported by grants from the Medical Research
Council (G0400126); The Wellcome Trust (084730); UCLH
CRDC (F136); the National Institute for Health Research
(08-08-SCC); the National Society for Epilepsy. This work was
partly undertaken at UCLH/UCL, which received a proportion of
funding from the Department of Health’s NIHR Biomedical
Research Centres funding scheme; The collection of the Irish pa-
tient cohort was supported by the Irish Higher Education Authority
Programme for Research in Third Level Institutions (PRTLI3); phe-
notyping by a Science Foundation Ireland Research Frontiers
Programme award (08/RFP/GEN1538); GlaxoSmithKline funded
the recruitment and phenotypic data collection of the GenEpA
Consortium samples used in this study and contributed to the
Table 5
Results of gene ontology analysis for partial epilepsies associated SNPs with genotyping costs associated with their study; the collection of the
Belgian patients was supported by the Funds National de la
Recherche Scientifique, grant no. FC 63574/3.4.620.06 F and the
Fondation Erasme, Universite
́
Libre de Bruxelles; Funding support
for Study of Irish Amyotrophic Lateral Sclerosis was provided by
Muscular Dystrophy Association, USA; Irish Institute of Clinical
Neurosciences Travel Award; and National Institutes of Health,
USA and the genotyping of samples was provided by the
National Institute of Neurological Disorders and Stroke (NINDS).
The dataset used for the analyses described in this manuscript was
obtained from the NINDS Database found at http://www.ncbi
.nlm.nih.gov/gap through dbGaP accession number
phs000127.v1.p1 | en |
dc.format.extent | 2136 | en |
dc.format.extent | 2147 | en |
dc.relation.ispartofseries | Brain | en |
dc.relation.ispartofseries | 133 | en |
dc.relation.ispartofseries | 7 | en |
dc.rights | Y | en |
dc.subject | partial epilepsy; genome-wide association; genetics; common variants | en |
dc.subject.lcsh | partial epilepsy; genome-wide association; genetics; common variants | en |
dc.title | Common genetic variation and susceptibility to partial epilepsies: A genome-wide association study | en |
dc.type | Journal Article | en |
dc.contributor.sponsor | Science Foundation Ireland (SFI) | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/cdohert | en |
dc.identifier.rssinternalid | 102986 | en |
dc.identifier.doi | http://dx.doi.org/10.1093/brain/awq130 | en |
dc.rights.ecaccessrights | openAccess | |
dc.contributor.sponsorGrantNumber | 08/RFP/GEN1538 | en |
dc.identifier.rssuri | http://www.scopus.com/inward/record.url?eid=2-s2.0-77954356949&partnerID=40&md5=64101d95458f5a18a3ff2b7c0a5ec5ae | en |