PTU was specifically associated with 32 independent SNPs in 12 loci (Supplemental Figure 3C; Supplemental Table 10 and 11). The top SNP was rs10519203 (p=5.12e-267) in HYKK and a robust eQTL for CHRNA5; the signal is likely driven by the CHRNA5 missense variant, rs16969968 (p=2.79e-175), which has previously been linked to tobacco use (r2= .87)12. Several other SNPs were closest to genes encoding nicotinic acetylcholine receptors, including CHRNA4, CHRNB4, CHRNB3, and CHRNB2 (Supplemental Table 10). Gene-based enrichment implicated multiple pathways and gene sets related to nicotinic acetylcholine receptors (Supplemental Table 12). Specific dopamine-related associations were also noted (e.g., PDE1C: rs215600; p=2.35e-18; DBH: rs1108581; p=1.00e-14).
