Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement

Abstract

Despite evidence of substantial comorbidity between psychiatric disorders and substance involvement, the extent to which common genetic factors contribute to their co-occurrence remains understudied. In the current study, we tested for associations between polygenic risk for psychiatric disorders and substance involvement (i.e., ranging from ever-use to severe dependence) among 2573 non-Hispanic European–American participants from the Study of Addiction: Genetics and Environment. Polygenic risk scores (PRS) for cross-disorder psychopathology (CROSS) were generated based on the Psychiatric Genomics Consortium’s Cross-Disorder meta-analysis and then tested for associations with a factor representing general liability to alcohol, cannabis, cocaine, nicotine, and opioid involvement (GENSUB). Follow-up analyses evaluated specific associations between each of the five psychiatric disorders which comprised CROSS—attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (AUT), bipolar disorder (BIP), major depressive disorder (MDD), and schizophrenia (SCZ)—and involvement with each component substance included in GENSUB. CROSS PRS explained 1.10% of variance in GENSUB in our sample (p < 0.001). After correction for multiple testing in our follow-up analyses of polygenic risk for each individual disorder predicting involvement with each component substance, associations remained between: (A) MDD PRS and non-problem cannabis use, (B) MDD PRS and severe cocaine dependence, (C) SCZ PRS and non-problem cannabis use and severe cannabis dependence, and (D) SCZ PRS and severe cocaine dependence. These results suggest that shared covariance from common genetic variation contributes to psychiatric and substance involvement comorbidity.

Association Between Substance Use Disorder and Polygenic Liability to Schizophrenia

“…Importantly, a growing number of studies have begun to investigate shared genetic liability between schizophrenia and patterns of substance use. We recently found a statistically significant association between general liability for substance use disorder and polygenic risk for cross-disorder psychopathology (19). In addition, recent studies have described common genetic risk factors between schizophrenia and cannabis use (20, 21), and evidence for shared genetic factors between schizophrenia and smoking-related phenotypes (22, 23).…”

Strong interactions between learned helplessness and risky decision-making in a rat gambling model

“…Risky decision-making is a characteristic of depression and of addictive disorders, including problem gambling123456789. However it is not clear whether predisposition towards risky choices increases the likelihood of depressive disorders, whether the converse is the case, or whether the two traits are independently associated to a third factor.…”

Interleukin-17 Alteration in First-Episode Psychosis: A Meta-Analysis

“…Over the past decades, abnormal immune-inflammatory responses, especially aberrant levels of pro-inflammatory cytokines, have been found in patients with schizophrenia [4,5] and their relatives [6]. Furthermore, accumulating evidence has shown that immune-related genes confer susceptibility to schizophrenia [7,8]. Therefore, immune abnormalities may play an important role in the pathophysiology of schizophrenia.…”