Using polygenic risk scores to investigate the evolution of smoking and mental health outcomes in UK biobank participants.

Abstract

Mendelian randomization studies report a bi-directional relation between cigarette smoking and mental disorders, yet from a clinical standpoint, mental disorders are the focus of treatment. Here, we used an event history framework to understand their evolution in the life course. Our objective was to estimate the relative contribution of genetic predispositions and self-reported smoking status (never, former, and present smoker) to hospitalizations for major depression, bipolar disorder, and schizophrenia. We calculated polygenic risk scores (PRS) for ever smoking, pack-years of smoking as a proportion of adult life, and neuroticism in 337,140 UK Biobank participants of white British ancestry. These PRS and self-reported smoking status were entered as explanatory variables in survival models for hospitalization. The estimated single nucleotide polymorphisms heritabilities (h2 ) were 23%, 5.7%, and 5.7% for pack-years, ever smoking, and neuroticism respectively. PRS pack-years and PRS neuroticism were associated with higher hospitalization risk for mental disorders in all smoking status groups. The hazard for mental health hospitalization was higher in both previous (HR: 1.50, CI: 1.35-1.67) and current (HR: 3.58, 2.97-4.31) compared to never smokers, after adjusting for confounders. Since genetic liabilities for smoking and neuroticism are fixed at conception and smoking initiation generally started before age 20, our results show that preventing smoking in adolescents probably prevents the development of mental disorders.