title: A Test-Replicate Approach to Candidate Gene Research on Addiction and Externalizing Disorders: A Collaboration Across Five Longitudinal Studies.
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.
authors.affiliation: Department of Human Development and Family Studies, Auburn University, 203 Spidle Hall, Auburn, AL, 36849, USA. di.samek@gmail.com.
authors.forename: Diana R
authors.initials: DR
authors.lastname: Samek
authors.affiliation: School of Social Work, University of Washington, Seattle, WA, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bailey
authors.affiliation: School of Social Work, University of Washington, Seattle, WA, USA.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Hill
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Sylia
authors.initials: S
authors.lastname: Wilson
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Keyes
authors.affiliation: School of Social Work, University of Washington, Seattle, WA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Epstein
authors.affiliation: Institute for Behavior Genetics, University of Colorado, Boulder, CO, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Smolen
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Miller
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Ken C
authors.initials: KC
authors.lastname: Winters
authors.affiliation: School of Social Work, University of Washington, Seattle, WA, USA.
authors.forename: J David
authors.initials: JD
authors.lastname: Hawkins
authors.affiliation: School of Social Work, University of Washington, Seattle, WA, USA.
authors.forename: Richard F
authors.initials: RF
authors.lastname: Catalano
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: William G
authors.initials: WG
authors.lastname: Iacono
authors.affiliation: Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: McGue
mesh_terms: D000293:Adolescent; D016739:Behavior, Addictive / Q000235:genetics*; D002648:Child; D003299:Cooperative Behavior; D005260:Female; D005789:Genealogy and Heraldry; D056726:Genetic Association Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D015203:Reproducibility of Results; D019966:Substance-Related Disorders / Q000235:genetics*
keywords: Addiction; Alcohol; Candidate gene studies; Cannabis; Externalizing disorders; Nicotine; Replication studies; Substance use disorders