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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.

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.

SUBMITTER: Vrieze SI

PROVIDER: S-EPMC3407593 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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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.

Vrieze Scott I SI McGue Matt M Iacono William G WG

Human genetics 20120411 6

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 SN ...[more]

PMID: 22492059

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Project description:Although lower socioeconomic status has been linked to increased youth substance use, much less research has determined potential mechanisms explaining the association. The current longitudinal study tested whether alternative (i.e., pleasure gained from activities without any concurrent use of substances) and complementary (i.e., pleasure gained from activities in tandem with substance use) reinforcement mediate the link between lower socioeconomic status and youth substance use. Further, we tested whether alternative and complementary reinforcement and youth substance use gradually unfold over time and then intersect with one another in a cascading manner. Potential sex differences are also examined. Data were drawn from a longitudinal survey of substance use and mental health among high school students in Los Angeles. Data collection involved four semiannual assessment waves beginning in fall 2013 (N = 3395; M baseline age = 14.1; 47% Hispanic, 16.2% Asian, 16.1% multiethnic, 15.7% White, and 5% Black; 53.4% female). The results from a negative binomial path model suggested that lower parental socioeconomic status (i.e., lower parental education) was significantly related to an increased number of substances used by youth. The final path model revealed that the inverse association was statistically mediated by adolescents' diminished engagement in pleasurable substance-free activities (i.e., alternative reinforcers) and elevated engagement in pleasurable activities paired with substance use (i.e., complementary reinforcers). The direct effect of lower parental education on adolescent substance use was not statistically significant after accounting for the hypothesized mediating mechanisms. No sex differences were detected. Increasing access to and engagement in pleasant activities of high quality that do not need a reinforcement enhancer, such as substances, may be useful in interrupting the link between lower parental socioeconomic status and youth substance use.

Project description:BackgroundReducing meat consumption is often advised; however, inadvertent nutritional deficiencies during pregnancy may result in residual neurodevelopmental harms to offspring. This study assessed possible effects of maternal diets in pregnancy on adverse substance use among adolescent offspring.MethodsPregnant women and their 13-year-old offspring taking part in a prospective birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), provided Food Frequency Questionnaire data from which dietary patterns were derived using principal components analysis. Multivariable logistic regression models including potential confounders evaluated adverse alcohol, cannabis, and tobacco use of the children at 15 years of age.ResultsLower maternal meat consumption was associated with greater problematic substance use among 15-year-old offspring in dose-response patterns. Comparing never to daily meat consumption after adjustment, risks were greater for all categories of problem substance use: alcohol, odds ratio OR = 1.75, 95% CI = (1.23, 2.56), p < 0.001; tobacco use OR = 1.85, 95% CI = (1.28, 2.63), p < 0.001; and cannabis OR = 2.70, 95% CI = (1.89, 4.00), p < 0.001. Given the likelihood of residual confounding, potential causality was evaluated using stratification for maternal allelic variants that impact biological activity of cobalamin (vitamin B12) and iron. Lower meat consumption disproportionally increased the risks of offspring substance misuse among mothers with optimally functional (homozygous) variants (rs1801198) of the gene transcobalamin 2 gene (TCN2) which encodes the vitamin B12 transport protein transcobalamin 2 implicating a causal role for cobalamin deficits. Functional maternal variants in iron metabolism were unrelated to the adverse substance use. Risks potentially attributable to cobalamin deficits during pregnancy include adverse adolescent alcohol, cannabis, and tobacco use (14, 37, and 23, respectively).ConclusionsLower prenatal meat consumption was associated with increased risks of adolescent substance misuse. Interactions between TCN2 variant status and meat intake implicate cobalamin deficiencies.

Dataset Information

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

Publications

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

Similar Datasets

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