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High‐density SNP screen of sodium channel genes by haplotype tagging and DNA pooling for association with idiopathic generalized epilepsy
Author(s) -
Makoff Andrew,
Lai Teck,
Barratt Catherine,
Valentin Antonio,
Moran Nick,
Asherson Philip,
Nashef Lina
Publication year - 2010
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2009.02473.x
Subject(s) - single nucleotide polymorphism , linkage disequilibrium , transmission disequilibrium test , genetics , haplotype , international hapmap project , bonferroni correction , proband , genetic association , biology , idiopathic generalized epilepsy , snp , allele , genotype , epilepsy , gene , mutation , statistics , mathematics , neuroscience
Summary We have investigated seven voltage‐gated sodium channel genes for association with idiopathic generalized epilepsy (IGE). Probands and control DNA were grouped into pools and used to screen 85 single‐nucleotide polymorphisms (SNPs), mostly HapMap SNPs tagging the common variation in these genes. Twelve SNPs exhibiting an allele frequency difference between pools were genotyped individually in our sample of 232 probands, 313 controls, and 95 parent–proband trios. Two SNPs, in SCN1A and SCN8A , were associated by allele and genotype at nominal level of significance, but were not significant after Bonferroni correction. Two SCN2A SNPs (rs3943809 and rs16850331) were associated by case–control with a subgroup with IGE and history of febrile seizures and also by transmission disequilibrium test (TDT) in parent–proband trios. Both SNPs are part of a linkage disequilibrium (LD) cluster of 38 SNPs, but none are obvious functional variants. The association of rs3943809 with the febrile seizure subgroup (p = 0.0004) remains significant after the conservative Bonferroni correction for multiple testing.