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Chunk #7 — METHODS — Statistical analyses

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Genetic overlap between Alzheimer's disease and Parkinson's disease at the MAPT locus.
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We used stepwise gatekeeper hypothesis testing 17 to identify SNPs associating with both PD and AD. We restricted our analyses to only those SNPs assayed in both GWASs from the IPDGC and the ADGC Consortia. First, we identified ‘pruned’ SNPs (removing all SNPs with r2 > 0.2, within 1 Mb of a given SNP) that were significant at a genome-wide level (p < 5 × 10 −8) within PD. Next, we evaluated the p-values of these PD genome-wide significant SNPs within the AD ADGC GWAS (Apolipoprotein E (APOE), age and sex co-varied summary statistic p-values) and applied a Bonferroni correction to control for multiple comparisons. Note that since the SNPs were a priori selected independently of the p-values from AD ADGC the proper Bonferroni correction is in terms of the number of PD genome-wide significant SNPs. Therefore, the p-value threshold for detecting significant ADGC loci controls for the number of PD genome-wide significant SNPs rather than p < 5 × 10 −8. It is important to note that this stepwise gatekeeper hypothesis testing approach implies a strict control for family-wise error rate in a multiple testing framework. 17