Our strongest association with a baseline factor was between rs472402 and factor F2 (Figure 3). This SNP is in the first intron of SRD5A1, which is expressed in the brain [76]. The protein product of this gene catalyzes the rate-limiting step in the production of the neurosteroid allopregnanolone [77], which is a GABAA agonist. Allopregnanolone has been shown to have anxiolytic effects in animals [78] and progesterone administration, perhaps because it is converted into allopregnanolone, has been shown to elicit mild sedative effects in humans [79], [80], [81]; these are broadly similar to the phenotypes that are associated with this SNP (Figure 2F). Another SNP (rs248797; Table S5) that is in strong LD with rs472402 (r2 = 0.73) has been identified as a cis-eQTL for the SRD5A1 gene in human monocytes [82] (P = 6×10−19) and is also in moderate LD (r2 = 0.3–0.7) with several SNPs that have been identified as cis-eQTLs for SRD5A1 in post-mortem samples from cerebellum and parietal cortex [83]. Rs472402 is also in strong LD with rs248793 (r2 = 0.89), which has been associated with
