Drinking and smoking polygenic risk is associated with neurodevelopmental outcomes of children and young adults independently of psychopathology and substance use.

Abstract

BackgroundAlcohol drinking and tobacco smoking are hazardous behaviors associated with a wide range of adverse health outcomes, including many mental and physical disorders. MethodsTo investigate the pleiotropic mechanisms linking these traits to cognitive and behavioral development, we explored the association of polygenic risk scores (PRS) related to drinks per week (DPW), age of smoking initiation (ASI), smoking initiation (SI), cigarettes per day (CPD), and smoking cessation (SC) with 433 neurodevelopmental features in 4,498 children and young adults of European ancestry from the Philadelphia neurodevelopmental cohort (PNC). This sample was not enriched for specific psychiatric traits, but 21% of the PNC participants endorsed substance use. ResultsAfter applying a false discovery rate multiple testing correction accounting for the number of PRS and traits tested, we identified 36 associations related to psychotic symptoms, emotion and age recognition social competencies, verbal reasoning, anxiety-related traits, parents education, and substance use. These associations were independent of the genetic correlations among the alcohol-drinking and tobacco-smoking traits and those with cognitive performance, educational attainment, risk-taking behaviors, and psychopathology. The removal of participants endorsing substance use did not affect the associations of each PRS with neurodevelopmental traits identified as significant in the discovery analyses. Gene-ontology enrichment analyses identified several neurobiological processes underlying mechanisms of the PRS associations we report. These were mainly related to brain connectivity. ConclusionsWe provide novel insights into the genetic overlap of smoking and drinking behaviors with neurodevelopment in children and young adults, highlighting their independence from psychopathology and other substance use.