Third, GenomicSEM analyses provided novel evidence suggesting greater genome‐wide genetic overlap between sensation seeking and alcohol consumption (r g = 0.29) than between sensation seeking and AUD (r g = 0.21). Although the magnitude of this difference was relatively small, mediation analyses demonstrated that after accounting for the genetic association with alcohol consumption, sensation seeking was not associated with AUD. These findings were consistent with local genetic correlation analyses highlighting both partial and complete overlap of genetic signal between sensation seeking and alcohol consumption at a much greater number of loci relative to AUD. Moreover, at the MVB12B‐LMX1B locus, which includes genes with critical roles in protein sorting with enriched expression in brain tissues (MVB12B) 39 and midbrain dopaminergic neuronal differentiation and survival (LMX1B), 63 the observed correlation between sensation seeking and AUD was largely accounted for by the relation of alcohol consumption with sensation seeking. These results demonstrate that genetic influences underlying associations between sensation seeking and AUD are largely mediated by increased alcohol consumption, consistent with prior neurobiological models relevant to addiction (e.g., dual‐systems and ‘addiction cycle’ models 8 , 11 ) and phenotypic research emphasising this pathway in early drinking experiences. 2 , 3 , 8
