Relationship between mood disorders and substance involvement and the shared genetic liabilities: A population-based study in Taiwan

Background: This study explored the phenotypic association of mood disorders, including major depressive disorder (MDD) and bipolar disorder (BPD), with a range of substance involvement, including lifetime experience and age at initiation of tobacco, alcohol, and betel nut use. Additionally, we elucidated polygenic risk score (PRS) association. Methods: In total, 132,615 community participants were recruited from the Taiwan Biobank. Genome-wide genotyping data were available for 106,806 unrelated individuals, and the PRS for MDD and BPD was calculated. The significance of mood disorders and PRSs associated with substance involvement were evaluated using a linear/logistic regression model with adjustment for potential confounders. Sex differences were assessed. Results: MDD and BPD were associated with regular alcohol consumption, drinking cessation, tobacco smoking, smoking cessation, betel nut chewing, and earlier onset of drinking. BPD was associated with an earlier onset of smoking. MDD PRS was associated with regular alcohol use (odds ratio [OR] per standard deviation increase in PRS = 1.03, p = 0.018), alcohol cessation (OR = 1.05, p = 0.03), regular tobacco use (OR = 1.08, p < 0.0001), and betel nut chewing (OR = 1.06, p < 0.0001), whereas BPD PRS was not associated with substance use. Phenotypic association strengths between MDD/BPD and regular drinking/smoking and the polygenic association between MDD PRS and regular smoking were larger in females than in males. Limitations: Retrospective self-reported MDD/BPD diagnoses and substance involvement. Conclusions: Mood disorders were associated with a range of substance involvement. Shared genetic architecture contributed to the co-occurrence of MDD and substance involvement. These findings may help design prevention and cessation strategies for substance use.