In particular, GWAS signals are enriched within regions of open chromatin identified by deoxyribonuclease I (DNase I) mapping (Maurano et al., 2012). These so-called DNase I hypersensitive sites (DHS) are regions where DNA is highly accessible (Bell et al., 2011), and likely serves some cis-regulatory function (Thurman et al., 2012). The location of DHS signals overlaps that of many other regulatory markers, indicating that they are a broad, non-specific marker of sites of active regulatory DNA, capturing many different ongoing biological processes affecting gene expression. The enrichment of significant GWAS associations in these regions provides some biological coherence for interpreting the functional impact of variation in these non-coding variants, and also suggest that SNPs located in DHSs (referred to as DHS SNPs) may be more likely to be “true” signals and less likely to be false positives. For this reason, we hypothesized that functional annotation information like DHS location could be used to improve the predictive ability of polygenic scores. Using alcohol problems as our primary outcome, we expected that polygenic scores based on SNPs in regulatory regions (DHSs) would
