As indicated by CADD scores, lead SNPs are overall not predicted to be deleterious. Only rs145005509 has a CADD score >10; this SNP is intronic to a predicted locus and upstream of an open reading frame, thus its functional significance is unclear. Importantly, we evaluated only common alleles, which are relatively infrequently deleterious. Perhaps more interestingly, lead SNPs are not predicted to have clear regulatory functions, in contrast with findings for schizophrenia (Roussos et al., 2014), major depression (Wray and Sullivan, 2017), and nicotine dependence (Zanger and Schwab, 2013). RegulomeDB annotations were only obtained for lead SNPs through the FUMA pipeline, leaving open the possibility that less strongly implicated markers have regulatory functions.
