A Test-Replicate Approach to Candidate Gene Research on Addiction and Externalizing Disorders: A Collaboration Across Five Longitudinal Studies

Diana R. Samek, Jennifer Bailey, Karl G. Hill, Sylia Wilson, Susanne Lee, Margaret A. Keyes, Marina Epstein, Andrew Smolen, Michael Miller, Ken C. Winters, J. David Hawkins, Richard F. Catalano, William G. Iacono, Matt McGue

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

This study presents results from a collaboration across five longitudinal studies seeking to test and replicate models of gene–environment interplay in the development of substance use and externalizing disorders (SUDs, EXT). We describe an overview of our conceptual models, plan for gene–environment interplay analyses, and present main effects results evaluating six candidate genes potentially relevant to SUDs and EXT (MAOA, 5-HTTLPR, COMT, DRD2, DAT1, and DRD4). All samples included rich longitudinal and phenotypic measurements from childhood/adolescence (ages 5–13) through early adulthood (ages 25–33); sample sizes ranged from 3487 in the test sample, to ~600–1000 in the replication samples. Phenotypes included lifetime symptom counts of SUDs (nicotine, alcohol and cannabis), adult antisocial behavior, and an aggregate externalizing disorder composite. Covariates included the first 10 ancestral principal components computed using all autosomal markers in subjects across the data sets, and age at the most recent assessment. Sex, ancestry, and exposure effects were thoroughly evaluated. After correcting for multiple testing, only one significant main effect was found in the test sample, but it was not replicated. Implications for subsequent gene–environment interplay analyses are discussed.

Original languageEnglish (US)
Pages (from-to)608-626
Number of pages19
JournalBehavior genetics
Volume46
Issue number5
DOIs
StatePublished - Sep 1 2016

Keywords

  • Addiction
  • Alcohol
  • Candidate gene studies
  • Cannabis
  • Externalizing disorders
  • Nicotine
  • Replication studies
  • Substance use disorders

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