Abstract: A Test-Replicate Approach to Candidate Gene Research on Addiction and Externalizing Disorders: A Collaboration Across Four Longitudinal Studies (Society for Prevention Research 23rd Annual Meeting)

Schedule:

Thursday, May 28, 2015

Columbia Foyer (Hyatt Regency Washington)

* noted as presenting author

Diana R. Samek, PhD, Assistant Professor, Auburn University, Montgomery, Auburn, Alabama, AL

Jennifer A. Bailey, PhD, Research Scientist, University of Washington, Seattle, WA

Karl G. Hill, PhD, Research Associate Professor, University of Washington, Social Development Research Group, Seattle, WA

Margaret Keyes, PhD, Investigator, University of Minnesota-Twin Cities, Minneapolis, MN

Susanne Seung-Eun Lee, PhD, Assistant Professor, University of Minnesota, Minneapolis, MN

Michael Miller, PhD, Investigator, University of Minnesota-Twin Cities, Minneapolis, MN

William G. Iacono, PhD, Professor, University of Minnesota-Twin Cities, Minneapolis, MN

Matthew McGue, PhD, Professor, University of Minnesota-Twin Cities, Minneapolis, MN

INTRODUCTION: Since the early 2000s, research into gene-environment interactions has been at times, very exciting, and at other times, substantially disappointing. In response to the calls for collaboration on studies investigating gene-environment interactions, this study represents a major step involved in an on-going collaboration between four longitudinal studies investigating the etiology of substance use disorders (SUDs) and related psychopathology. Using data from four separate studies, we evaluate associations between SUDs and six candidate genes that prior research suggests are relevant to SUDs (MAOA, 5HTTLPR, DRD2, DAT1, DRD4, and COMT).

METHOD: The test sample included youth from the Minnesota Center for Twin and Family Research (MCTFR, N=3,487, ages assessed 11-29). The replication samples included the Seattle Social Development Project (SSDP, N=808, ages assessed 10-33), Raising Health Children (RHC, N=1,040, ages assessed 5-25), and the Minnesota Drug Abuse and ADHD study (MN Study, N=676, ages assessed 13-31). 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 principle components of ethnic ancestry computed using all autosomal markers in subjects across the four data sets, and age at the most recent assessment. A Bonferonni correction was used to control for multiple testing (.05/6 = .008) and sex/ethnicity differences were evaluated.

RESULTS: In the test sample (MCTFR), we found an association between DAT1 and cannabis use disorder for white subjects who had been exposed (i.e., had ever used cannabis; β = .09, p < .006). In analyses looking at males and females separately, a pattern emerged supporting the risk allele hypothesis for DRD4 and DAT1 for nicotine and alcohol for males. The strongest effects were for white males who had ever used the respective substance (β’s ranged from .09-.11, p’s from .01-.03). Replication analyses in the SSDP, RHC and the MN Study samples are underway, and full study findings will be presented at SPR.

SIGNIFICANCE: This study represents a major step forward by implementing a collaboration across multiple longitudinal studies to investigate the genetic contributions to the etiology of substance use disorder and related psychopathology. The approach provides a framework for moving beyond a reliance on single study false-positives that have been the source of concern in recent reviews.

Abstract: A Test-Replicate Approach to Candidate Gene Research on Addiction and Externalizing Disorders: A Collaboration Across Four Longitudinal Studies (Society for Prevention Research 23rd Annual Meeting)

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