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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.

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Notes

  1. Note that we also conducted all analyses with a subsample of individuals who, at any one assessment where either (1) a current smoker or (2) had been a smoker in the past. Current smoker was defined just as in the current smoking sample described in the text. To be a past smoker, we required that an individual report smoking on average one cigarette per day for 12 months. The results from this sample did not change in any significant way.

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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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  1. University of Minnesota, 75 East River Road, Minneapolis, MN, 55455, USA

    Scott I. Vrieze, Matt McGue & William G. Iacono

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  1. Scott I. Vrieze
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Correspondence to Scott I. Vrieze.

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Vrieze, S.I., McGue, M. & Iacono, W.G. The interplay of genes and adolescent development in substance use disorders: leveraging findings from GWAS meta-analyses to test developmental hypotheses about nicotine consumption. Hum Genet 131, 791–801 (2012). https://doi.org/10.1007/s00439-012-1167-1

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