Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood

Joseph D. Deak, D. Angus Clark, Mengzhen Liu, Jonathan D Schaefer, Seon-Kyeong Jang, C. Emily Durbin, William G. Iacono, Matt McGue, Scott Vrieze, Brian M. Hicks

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background and Aims: Molecular genetic studies of alcohol and nicotine use have identified many genome-wide association study (GWAS) loci. We measured associations between drinking and smoking polygenic scores (PGS) and trajectories of alcohol and nicotine use outcomes from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied for consumption versus problematic substance use. Design, setting, participants and measurements: We fitted latent growth curve models with structured residuals to scores on measures of alcohol and nicotine use and problems from ages 14 to 34 years. We then estimated associations between the intercept (initial status) and slope (rate of change) parameters and PGSs for drinks per week (DPW), problematic alcohol use (PAU), cigarettes per day (CPD) and ever being a regular smoker (SMK), controlling for sex and genetic principal components. All data were analyzed in the United States. PGSs were calculated for participants of the Minnesota Twin Family Study (n = 3225) using results from the largest GWAS of alcohol and nicotine consumption and problematic use to date. Findings: Each PGS was associated with trajectories of use for their respective substances [i.e. DPW (βmean = 0.08; βrange = 0.02–0.12) and PAU (βmean = 0.12; βrange = −0.02 to 0.31) for alcohol; CPD (βmean = 0.08; βrange = 0.04–0.14) and SMK (βmean = 0.18; βrange = 0.05–0.36) for nicotine]. The PAU and SMK PGSs also exhibited cross-substance associations (i.e. PAU for nicotine-specific intercepts and SMK for alcohol intercepts and slope). All identified SMK PGS effects remained as significant predictors of nicotine and alcohol trajectories (βmean = 0.15; βrange = 0.02–0.33), even after adjusting for the respective effects of all other PGSs. Conclusions: Substance use-related polygenic scores (PGSs) vary in the strength and generality versus specificity of their associations with substance use and problems over time. The regular smoking PGS appears to be a robust predictor of substance use trajectories and seems to measure both nicotine-specific and non-specific genetic liability for substance use, and potentially externalizing problems in general.

Original languageEnglish (US)
Pages (from-to)1117-1127
Number of pages11
Issue number4
StatePublished - Apr 2022

Bibliographical note

Funding Information:
This work was supported by United States Public Health Service grants R37 AA09367 (M.M.), R01 AA024433 (B.M.H.), T32 AA007477 (B.M.H.) and T32 AA028259 (J.D.D.) from the National Institute of Alcohol Abuse and Alcoholism and R01 DA034606 (B.M.H.), R37 DA005147 (W.G.I.), R01 DA013240 (W.G.I.), R01 DA044283 (S.I.V.), R01 DA037904 (S.I.V.), R01 DA042755 (M.M./S.I.V.) and U01 DA046413 (S.I.V.) from the National Institute on Drug Abuse.

Publisher Copyright:
© 2021 Society for the Study of Addiction


  • Alcohol
  • developmental trajectories
  • nicotine
  • polygenic risk scores
  • smoking
  • substance use

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural


Dive into the research topics of 'Alcohol and nicotine polygenic scores are associated with the development of alcohol and nicotine use problems from adolescence to young adulthood'. Together they form a unique fingerprint.

Cite this