In summary, we report one GWS association signal, represented by rs115455482 and rs74722579 (r2 ≥ 0.95 in EAs; rs74722579 is a common variant in both EAs and AAs) at the CHRM3 locus, with Ca-HL. The findings were GWS in our Yale-Penn 1 taken separately, with nominally significant associations of two variants in one of two other available samples of EAs. Additional support was obtained for rs74722579 in the meta-analysis of AA samples. Our findings are consistent with a model in which the regulatory variant rs115455482 affects the expression of CHRM3 in THAL, which could alter the stimulatory efficiency of cannabis on hallucinations, a potential underlying mechanism for its association with Ca-HL. Validation of these findings and the putative mechanism is warranted to increase our understanding of the biology of Ca-HL.
