In the trans-ancestry GWAS meta-analysis of OEcontrols, we observed an additional single-variant GWS association, rs12461856 on chromosome 19 (z=−5.61, p=2.1×10−8; Figure 1C; Table 1). With respect to this locus, no heterogeneity was observed among the cohorts included in the meta-analysis (heterogeneity: I2=0, p=0.554; Supplementary Table 6). This variant did not show significant genetic associations with traits related to other addictive substances (Supplementary Table 3). In the UK Biobank, no novel phenotypic associations with rs12461856 survived multiple testing correction (FDR q<0.05; Figure 3, bottom panel; Supplementary Table 7). A gene-based GWS association was identified for SDCCAG8 on chromosome 1 (p=1.4×10−6, Table 1; Supplementary Figure 1C). In the gene-based phenome-wide scan, we observed 77 traits associated with SDCCAG8 that survived multiple testing correction (p<1.05×10−5; Supplementary Table 8). Among them, we observed strong associations for schizophrenia (p=2.5×10−12) and risk taking (p=1.1×10−9). With respect to the molecular pathways, significant enrichments were also observed for GO:0017069~small RNA binding (beta=0.65, p=5.4×10−7) and a curated gene set related to genes downregulated 6 h after induction of HoxA5 expression in a breast cancer cell line (Standard name: CHEN_HOXA5_TARGETS_6HR_DN; beta=1.37, p=8.6×10−6).
