The interplay of genes and adolescent development in substance use disorders: Leveraging findings from GWAS meta-analyses to test developmental hypotheses about nicotine consumption

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Abstract

The present study evaluated gene by development interaction in cigarettes smoked per day (CPD) in a longitudinal community-representative sample (N = 3,231) of Caucasian twins measured at ages 14, 17, 20, and 24. Biometric heritability analyses show strong heritabilities and shared environmental influences, as well as cross-age genetic and shared environmental correlations. Single nucleotide polymorphisms (SNPs) previously associated with CPD according to meta-analysis were summed to create a SNP score. At best, the SNP score accounted for 1 % of the variance in CPD. The results suggest developmental moderation with a larger significant SNP score effect on CPD at ages 20 and 24, and smaller non-significant effect at ages 14 and 17. These results are consistent with the notion that nicotine-specific genetic substance use risk is less important at younger ages, and becomes more important as individuals age into adulthood. In a complementary analysis, the same nicotine-relevant SNP score was unrelated to the frequency of alcohol use at ages 14, 17, 20, or 24. These results indicate that the SNP score is specific to nicotine in this small sample and that increased exposure to nicotine at ages 20 and 24 does not influence the extent of concurrent or later alcohol use. Increased sample sizes and replication or meta-analysis are necessary to confirm these results. The methods and results illustrate the importance and difficulty of considering developmental processes in understanding the interplay of genes and environment.

Original languageEnglish (US)
Pages (from-to)791-801
Number of pages11
JournalHuman Genetics
Volume131
Issue number6
DOIs
StatePublished - Jun 2012

Bibliographical note

Funding Information:
Acknowledgments This work was supported by grants R37 DA 05147, R01 DA 13240, and U01 DA 024417 of the National Institute on Drug Abuse; R01 AA 09367 of the National Institute on Alcohol Abuse and Alcoholism; and 5T32 MH 017069 (Vrieze) of the National Institute of Mental Health.

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