The overarching goals of this proposal are twofold: 1) to support the candidate in gaining additional training in the use of molecular and statistical genetic methods to identify risk alleles for substance use disorders (SUD), and 2) conduct a genome wide association study (GWAS) for a novel phenotype, a pre-morbid liability index for SUDs, and replication studies in two independent samples. The advantage of focusing on indicators of pre-morbid risk (i.e. prior to initiation of substance use) is that analyses are based on underlying rather than expressed risk and so may provide a more sensitive measure of genetic liability than manifest or "post-morbid" measures of SUDs. Focusing on pre-morbid liability also provides a sound theoretical framework to examine developmental processes associated with the emergence of SUDs such as exposure to environmental risk (gene-environment correlations) and sensitivity to environmental adversity (gene x environment interactions). The training portion of the proposal focuses on gaining skills in bioinformatics to identify candidate gene systems and select informative polymorphisms (e.g. SNPs) as well as expertise in statistical analyses to detect associations between genetic markers and complex phenotypes such as SUDs. The research plan entails conducting a GWAS of 61 OK SNPs on a measure of pre-morbid liability to SUDs on approximately 6000 participants. Replication studies of significant findings from the GWAS will then be conducted in two independent samples of high-risk youth. The research plan also includes studies examining mechanisms of G-E interplay that underlie the development of SUDs by utilizing a longitudinal twin design. The award will also assist the candidate in pursuing his long-term goal of becoming an independent researcher and is likely to yield important insights into the etiology of SUDs.

Public Health Relevance

We propose a novel approach to identifying genes associated with substance abuse by focusing on risk factors present prior to initiation of substance use. Pooling multiple longitudinal samples (N~6000), we will conduct a genome wide association study on a novel measure of pre-morbid risk for substance abuse to identify specific risk genes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DA025868-05
Application #
8477159
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Weinberg, Naimah Z
Project Start
2009-09-30
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$181,360
Indirect Cost
$13,434
Name
University of Michigan Ann Arbor
Department
Psychiatry
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Durbin, C Emily; Hicks, Brian M; Blonigen, Daniel M et al. (2016) Personality trait change across late childhood to young adulthood: Evidence for nonlinearity and sex differences in change. Eur J Pers 30:31-44
Samek, D R; Hicks, B M; Keyes, M A et al. (2015) Gene-environment interplay between parent-child relationship problems and externalizing disorders in adolescence and young adulthood. Psychol Med 45:333-44
Wilson, S; Hicks, B M; Foster, K T et al. (2015) Age of onset and course of major depressive disorder: associations with psychosocial functioning outcomes in adulthood. Psychol Med 45:505-14
Blonigen, Daniel M; Durbin, C Emily; Hicks, Brian M et al. (2015) Alcohol use initiation is associated with changes in personality trait trajectories from early adolescence to young adulthood. Alcohol Clin Exp Res 39:2163-70
Foster, K T; Hicks, B M; Iacono, W G et al. (2015) Gender differences in the structure of risk for alcohol use disorder in adolescence and young adulthood. Psychol Med 45:3047-58
Samek, Diana R; Hicks, Brian M (2014) Externalizing Disorders and Environmental Risk: Mechanisms of Gene-Environment Interplay and Strategies for Intervention. Clin Pract (Lond) 11:537-547
Hicks, Brian M; Iacono, William G; McGue, Matt (2014) Identifying childhood characteristics that underlie premorbid risk for substance use disorders: socialization and boldness. Dev Psychopathol 26:141-57
Durbin, C Emily; Hicks, Brian M (2014) Personality and Psychopathology: A Stagnant Field in Need of Development. Eur J Pers 28:362-386
Hicks, Brian M; Johnson, Wendy; Durbin, C Emily et al. (2014) Delineating selection and mediation effects among childhood personality and environmental risk factors in the development of adolescent substance abuse. J Abnorm Child Psychol 42:845-59
Foster, Katherine T; Hicks, Brian M; Iacono, William G et al. (2014) Alcohol use disorder in women: Risks and consequences of an adolescent onset and persistent course. Psychol Addict Behav 28:322-35

Showing the most recent 10 out of 26 publications