The Role of A Priori–Identified Addiction and Smoking Gene Sets in Smoking Behaviors

Abstract Introduction Smoking is a leading cause of death, and genetic variation contributes to smoking behaviors. Identifying genes and sets of genes that contribute to risk for addiction is necessary to prioritize targets for functional characterization and for personalized medicine. Methods We pe...

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Bibliographic Details
Published in:Nicotine & tobacco research 2020-07, Vol.22 (8), p.1310-1315
Main Authors: Evans, Luke M, Johnson, Emma C, Melroy-Greif, Whitney E, Hewitt, John K, Hoeffer, Charles A, Keller, Matthew C, Saba, Laura M, Stitzel, Jerry A, Ehringer, Marissa A
Format: Article
Language:English
Subjects:
Age of Onset
Behavior, Addictive - epidemiology
Behavior, Addictive - genetics
Behavior, Addictive - psychology
Colorado - epidemiology
Genetic Markers
Genome-Wide Association Study
Humans
Original Investigations
Phenotype
Polymorphism, Single Nucleotide
Receptors, Nicotinic - genetics
Smoking - epidemiology
Smoking - genetics
Smoking - psychology
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Summary:Abstract Introduction Smoking is a leading cause of death, and genetic variation contributes to smoking behaviors. Identifying genes and sets of genes that contribute to risk for addiction is necessary to prioritize targets for functional characterization and for personalized medicine. Methods We performed a gene set–based association and heritable enrichment study of two addiction-related gene sets, those on the Smokescreen Genotyping Array and the nicotinic acetylcholine receptors, using the largest available GWAS summary statistics. We assessed smoking initiation, cigarettes per day, smoking cessation, and age of smoking initiation. Results Individual genes within each gene set were significantly associated with smoking behaviors. Both sets of genes were significantly associated with cigarettes per day, smoking initiation, and smoking cessation. Age of initiation was only associated with the Smokescreen gene set. Although both sets of genes were enriched for trait heritability, each accounts for only a small proportion of the single nucleotide polymorphism-based heritability (2%–12%). Conclusions These two gene sets are associated with smoking behaviors, but collectively account for a limited amount of the genetic and phenotypic variation of these complex traits, consistent with high polygenicity. Implications We evaluated evidence for the association and heritable contribution of expert-curated and bioinformatically identified sets of genes related to smoking. Although they impact smoking behaviors, these specifically targeted genes do not account for much of the heritability in smoking and will be of limited use for predictive purposes. Advanced genome-wide approaches and integration of other ‘omics data will be needed to fully account for the genetic variation in smoking phenotypes.
ISSN:1469-994X
1462-2203
1469-994X
DOI:10.1093/ntr/ntaa006