Drinking and smoking polygenic risk is associated with childhood and early-adulthood psychiatric and behavioral traits independently of substance use and psychiatric genetic risk

Renato Polimanti,Flavio De Angelis,Daniel S Tylee,Aranyak Goswami,Gita A Pathak,Joel Gelernter,Frank R Wendt

doi:10.1038/s41398-021-01713-z

Renato Polimanti, Flavio De Angelis + Show 5 more

Open Access

https://doi.org/10.1038/s41398-021-01713-z

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Abstract

Alcohol drinking and tobacco smoking are hazardous behaviors associated with a wide range of adverse health outcomes. In this study, we explored the association of polygenic risk scores (PRS) related to drinks per week, age of smoking initiation, smoking initiation, cigarettes per day, and smoking cessation with 433 psychiatric and behavioral traits in 4498 children and young adults (aged 8–21) of European ancestry from the Philadelphia neurodevelopmental cohort. After 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 psychiatric and behavioral traits identified as significant in the discovery analyses. Gene-ontology enrichment analyses identified several neurobiological processes underlying mechanisms of the PRS associations we report. In conclusion, we provide novel insights into the genetic overlap of smoking and drinking behaviors in children and young adults, highlighting their independence from psychopathology and substance use.

Highlights

Alcohol drinking and tobacco smoking may result in direct or indirect health concerns
To dissect the pleiotropic mechanisms related to alcohol drinking and tobacco smoking, we investigated their genetic liability through the polygenetic risk scores (PRS) derived from GSCAN genome-wide association data with respect to psychiatric and behavioral traits assessed in the Philadelphia Neurodevelopmental Cohort (PNC)
Considering other psychiatric, behavioral, and social traits (Supplementary Table S5), Phenotypic correlations among psychiatric and behavioral traits associated with smoking and drinking polygenic risk The polygenic risk drinking and smoking behaviors were tested with respect to 433 psychiatric and behavioral traits assessed in PNC children and young adults and a total of 36 phenotypes were significantly associated after accounting for the number of PRS and phenotypes tested (FDR < 5%; Table 1, Fig. 2 and Supplementary Table S6)

Summary

Introduction

Alcohol drinking and tobacco smoking may result in direct or indirect health concerns. Large-scale genome-wide association studies (GWAS) of traits related to alcohol drinking and tobacco smoking demonstrated that the predisposition to these complex behavioral traits is highly polygenic (i.e., thousands of variants with small effects) [6,7,8,9,10,11,12]. To dissect the pleiotropic mechanisms related to alcohol drinking and tobacco smoking, we investigated their genetic liability through the polygenetic risk scores (PRS) derived from GSCAN genome-wide association data with respect to psychiatric and behavioral traits assessed in the Philadelphia Neurodevelopmental Cohort (PNC). Similar to other studies [14,15,16,17,18,19,20], we used a high-resolution phenome-wide screening approach investigating hundreds of traits related to different

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