The interplay of genes and adolescent development in substance use disorders: leveraging findings from GWAS meta-analyses to test developmental hypotheses about nicotine consumption.
- Authors
- Vrieze, Scott I; McGue, Matt; Iacono, William G
- Year
- 2012
- Journal
- Human genetics
- PMID
- 22492059
- DOI
- 10.1007/s00439-012-1167-1
- PMCID
- PMC3407593
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.
Developmental Trajectory of Cigarettes Smoked per Day. The red line is a running mean. The green line is a running standard deviation. The dip at approximately age 17 is when the assessment protocol switched from a computerized questionnaire to an in-person interview.
Heatmap of Correlation Matrix and Heritability Components of CPD for the Full Sample and Subsample of Current Smokers. The figure is composed of two columns—the full sample is on the left and the subsample of current smokers is on the right. The upper two 4×4 matrices denoted “P” are the total phenotypic correlation matrices for each sample. Below that are the additive genetic (A), shared environmental (C), and unshared environmental (E) components for each sample. The matrices are scaled such that element-wise summation of the A, C, and E matrices gives the phenotypic (P) correlation matrix. This scaling gives the CPD heritabilities and environmental effects along the diagonal of the A, C, and E matrices (e.g., CPD is 31% heritable at age 14 in the full sample).
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