DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Epilepsy (remission after treatment). The EFO term response to drug, epilepsy was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: response to drug, epilepsy

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

D Speed, C Hoggart, S Petrovski, I Tachmazidou, A Coffey, A Jorgensen, H Eleftherohorinou, M De Iorio, M Todaro, T De, D Smith, PE Smith, M Jackson, P Cooper, M Kellett, S Howell, M Newton, R Yerra, M Tan, C French, M Reuber, GE Sills, D Chadwick, M Pirmohamed, D Bentley, I Scheffer, S Berkovic, D Balding, A Palotie, A Marson, TJ O'Brien, MR Johnson

TITLE:

A genome-wide association study and biological pathway analysis of epilepsy prognosis in a prospective cohort of newly treated epilepsy.

JOURNAL:

Human molecular genetics Jan 2014, Vol 23, pp. 247-58

ABSTRACT:

We present the analysis of a prospective multicentre study to investigate genetic effects on the prognosis of newly treated epilepsy. Patients with a new clinical diagnosis of epilepsy requiring medication were recruited and followed up prospectively. The clinical outcome was defined as freedom from seizures for a minimum of 12 months in accordance with the consensus statement from the International League Against Epilepsy (ILAE). Genetic effects on remission of seizures after starting treatment were analysed with and without adjustment for significant clinical prognostic factors, and the results from each cohort were combined using a fixed-effects meta-analysis. After quality control (QC), we analysed 889 newly treated epilepsy patients using 472 450 genotyped and 6.9 × 10(6) imputed single-nucleotide polymorphisms. Suggestive evidence for association (defined as Pmeta < 5.0 × 10(-7)) with remission of seizures after starting treatment was observed at three loci: 6p12.2 (rs492146, Pmeta = 2.1 × 10(-7), OR[G] = 0.57), 9p23 (rs72700966, Pmeta = 3.1 × 10(-7), OR[C] = 2.70) and 15q13.2 (rs143536437, Pmeta = 3.2 × 10(-7), OR[C] = 1.92). Genes of biological interest at these loci include PTPRD and ARHGAP11B (encoding functions implicated in neuronal development) and GSTA4 (a phase II biotransformation enzyme). Pathway analysis using two independent methods implicated a number of pathways in the prognosis of epilepsy, including KEGG categories 'calcium signaling pathway' and 'phosphatidylinositol signaling pathway'. Through a series of power curves, we conclude that it is unlikely any single common variant explains >4.4% of the variation in the outcome of newly treated epilepsy. PUBMED: 23962720
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