We also tested PRS derived from a large-scale GWAS of neuroticism (N=390,278)35. This behavioral trait represents a tendency to negative affect and was previously observed to be genetically correlated with several psychiatric disorders, including SUDs17, 40, major depression41, and posttraumatic stress disorder42. Consistent with our expectation of genetic liability to negative affect being related to dependence but not exposure alone, the neuroticism PRS was associated with dependence compared with unexposed (ODunexposed: Neffective=4,728, PT=0.001, z=4.16, p=3.2×10−5, FDR q=5.76×10−4) and dependence compared with exposed controls (ODexposed: Neffective=3,038, PT=0.001, z=3.1, p=0.002, FDR q=0.016), but not with exposed vs unexposed controls (OEcontrols: Neffective=5,376, PT=0.5, z=−0.42, p=0.671, FDR q=0.919).
