To evaluate the genetic overlap between CUD and a range of other phenotypes at the polygenic level, we conducted analyses of PRS for 22 phenotypes related to cognition, personality, psychiatric disorders, reproduction and smoking behaviour (Methods; list of references to the GWASs of the 22 phenotypes and results can be found in Supplementary Table 11). PRS for eight phenotypes (three measures of cognitive perfomance, age at first birth, life time smoking, ADHD, depressive symptoms and schizophrenia) demonstrated strong association with CUD (4.33x10−4< P <7.44x10−15; Figure 4 and Supplementary Table 11). Strikingly, PRS for measures of educational attainment by the Social Science Genetic Association Consortium (SSGAC) (educational years: z-score=−7.78; P=7.44x10−15; college completion: z-score=−5.10; P=3.33x10−7), were strongly negatively associated with the risk of CUD, a finding which was reinforced by the significant negative association of PRS for human intelligence with CUD (z-score=−3.51; P=4.33x10−4). Our results suggest an overlap in genetic risk factors with a decrease in the odds ratio for CUD with increased number of educational years/cognitive performance (Supplementary Figure 3A-C.). The observed decreased risk of CUD with increased age at first
