Analysis of Genome-Wide Association Study (GWAS) data looking for replicating signals in Alzheimer's disease (AD)

Abstract

We have performed cross-platform comparisons of output from 4 GWAS in late-onset Alzheimer's disease (LOAD) -- Reiman et al., 2007; Li et al., 2008; Beecham et al., 2008 and Carrasquillo et al., 2009 to search for new association signals. The aim was to reveal genes that replicated across studies and hence merit further investigation. All SNPs with p-values ranging between 5×10-5 - 5×10-8 from each study were assessed across the other studies (either directly or by using a perfect proxy when comparing data from different chip platforms). This revealed only a single SNP (rs929156 in the tripartite motif-containing protein 15, TRIM15, gene) that was replicating across all studies at a level approaching genome-wide significance (P = 8.77×10-8) and where meta-analysis of odds ratios showed a significant effect on risk (OR 1.1, 95% CI 1.0-1.2, P = 0.03). The vast majority of data analysed failed to replicate across these GWAS. The number of replicating association signals we observed is no higher than would be expected due to chance. However, increasing the power by using additional data from larger studies may enable this approach to identify potential LOAD candidate genes for confirmatory association studies.