Alongside recognition that there is no “gene for” AUD, but rather many contributing genes and common variants with small individual effect sizes, is the understanding that AUD shares genetic influences with numerous other psychiatric disorders and other traits/behaviors. 85 , 137 , 138 The rich phenotyping available in COGA has enabled a number of investigations into pleiotropy (i.e., when the same underlying genetic predisposition gives rise to multiple phenotypes) and genetic overlap among different substance use phenotypes and other relevant traits. For example, a study from Hartz et al. 139 tested whether polygenic scores for schizophrenia liability were associated with substance use disorder diagnoses in three ascertained datasets, one of which was COGA. They found that polygenic liability for schizophrenia was significantly associated with substance use disorder (SUD) diagnoses, suggesting that the high comorbidity observed between schizophrenia and SUDs may be in part due to shared genetic liability, although this could also represent evidence for a “self‐medication” hypothesis, whereby schizophrenia (and therefore genetic liability for schizophrenia) is associated with greater risk for SUDs.
