Computational protocol: Common genetic variation and susceptibility to partial epilepsies: a genome-wide association study

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Protocol publication

[…] Only SNPs present on both Illumina Human610-Quadv1 and Human1-2M-DuoCustom were included in the analysis. Association analysis was performed using PLINK (Purcell et al., ). First, we used the logistic regression additive model, including gender and all significant EIGENSTRAT axes, as assessed using the Tracy-Widom statistic with P < 0.05, as covariates into the model. Further, we performed a stratified analysis using the Cochran–Mantel–Haenszel test. For this analysis, seven strata were used, each corresponding to the recruitment country. To ensure homogeneity of each stratum, we performed principal component analysis within each stratum separately and removed the outliers.Only SNPs with minor allele frequency of 1% and above were included in the analysis. We chose this frequency cut-off because we were interested in common variants. Our study was underpowered to detect associations with lower allele frequencies. Genotypes of SNPs with minor allele frequency <1% were less reliably called across the different cohorts.Power calculations were performed using PGA Power Calculator software (Menashe et al., ) assuming a disease prevalence of 0.5%, the additive risk model, and r2 0.9 between a causal variant and a genotyped marker (). Figure 1Gene ontology analysis was performed using the ALIGATOR method (Holmans et al., ) to investigate whether there was enrichment for SNPs in genes in any gene ontology categories among the SNPs with low, but not genome-wide significant, P-values. We investigated these SNP sets using two thresholds, P < 0.0001 and P < 0.001. Only SNPs located within genes were included (based on NCBI SNP build 129 and NCBI sequence build 36.3). One SNP per gene, with the lowest P-value, was included in the ALIGATOR analysis using 20 000 simulated replicate gene lists and 5000 simulated replicate studies. […]

Pipeline specifications

Software tools PLINK, ALIGATOR
Application GWAS
Organisms Homo sapiens
Diseases Epilepsy