Systematic Review of Polygenic Gene–Environment Interaction in Tobacco, Alcohol, and Cannabis Use

• Published in: Behavior genetics Vol. 49; no. 4; pp. 349 - 365
• Main Authors: Pasman, Joëlle A., Verweij, Karin J. H., Vink, Jacqueline M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-07-2019; Springer Nature B.V
• Subjects: Alcohol; Alcohol Drinking - genetics; Alcohol use; Alleles; Behavioral Science and Psychology; Candidates; Cannabis; Clinical Psychology; Drug use; Ethanol; Etiology; Gene Frequency - genetics; Gene-Environment Interaction; Genetic diversity; Genetic factors; Genetic Predisposition to Disease - genetics; Haplotypes; Haplotypes - genetics; Health Psychology; Humans; Marijuana; Marijuana Use - genetics; Multifactorial Inheritance - genetics; Nicotiana; Psychology; Public Health; Review; Risk Factors; Substance abuse; Substance use; Susceptibility; Systematic review; Tobacco; Tobacco Use - genetics; Variants; Alcohol; Tobacco; Cannabis; Gene–environment interaction; Genetic risk; Polygenic risk
• ISSN: 0001-8244; 1573-3297
• DOI: 10.1007/s10519-019-09958-7

Studies testing the effect of single genetic variants on substance use have had modest success. This paper reviewed 39 studies using polygenic measures to test interaction with any type of environmental exposure (G×E) in alcohol, tobacco, and cannabis use. Studies using haplotype combinations, sum scores of candidate-gene risk alleles, and polygenic scores (PS) were included. Overall study quality was moderate, with lower ratings for the polygenic methods in the haplotype and candidate-gene score studies. Heterogeneity in investigated environmental exposures, genetic factors, and outcomes was substantial. Most studies (
N
 = 30) reported at least one significant G×E interaction, but overall evidence was weak. The majority (
N
 = 26) found results in line with differential susceptibility and diathesis-stress frameworks. Future studies should pay more attention to methodological and statistical rigor, and focus on replication efforts. Additional work is needed before firm conclusions can be drawn about the importance of G×E in the etiology of substance use.