Our findings must be interpreted in the context of the potential limitations. One limitation is that our results suggest potential mechanisms through which the variant sets may affect AD, rather than proving the mechanism. Possible next steps to test the suggested mechanisms include testing these variants sets in an independent sample and examining the function of significant sets in targeted laboratory experiments. We explored whether some of variants included in the top variants sets influenced gene expression using GTEx (Carithers and Moore, 2015) (Table S6) and found several variants are expression quantitative trait loci (eQTL). Other potential methods to explore the functional effects of these variants include targeted genome editing where the specific variant of interest is artificially engineered against a standard cell line background (e.g. CRISPR-Cas9) and the functional effects are observed (de Souza, 2012), or targeted chromatin immunoprecipitation (ChIP) assays of regulatory elements such as transcription factor binding sites and histone marks overlapping with the significant results.
