This application addresses the NIAAA Research Initiative to characterize the mechanisms of behavior change in drinking. Heavy alcohol use and alcohol use disorders (AUDs) peak between ages 18 and 25, representing a serious public health concern. It is estimated that roughly 50% of the risk for alcohol use disorders is genetic, and new technology has facilitated the identification of specific target genes that confer risk. In order to design effective early interventions, we must better understand the mechanisms through which target genes contribute to different patterns of drinking behavior. Involvement in multiple deviant behaviors (generalized deviance) and individual differences in alcohol response are established risk factors for later AUDs, and both are driven, at least in part, by genetic influences. The proposed study will address three major research aims: (1) Identify unique genetic associations with four different developmental trajectories of heavy drinking: Stable {High}, Late Increasing, Developmentally Limited, and Stable {Light}; (2) Identify genetic influences on individual differences in alcohol response in a laboratory-based, placebo-controlled alcohol challenge; and (3) Test alcohol response and generalized deviance as phenotypic mediators of the effects of five candidate genes on the four trajectories of heavy drinking. Our multi-method approach to these research aims is unique in four important respects. First, rather than rely on a cross-sectional sample, we will collect salivary DNA samples from an ethnically diverse prospective cohort (N = 1,060) who have previously reported on their alcohol use and other deviant behaviors (e.g., drug use, sexual risk-taking) across 10 waves of assessments from age 18 to 24. Second, we will capitalize on cutting-edge innovations in biotechnology that allow for cost- effective genotyping of candidate genes. We will focus on a panel of 63 polymorphisms in 5 candidate genes related to cholinergic (CHRM2), opioid (OPRM1), dopaminergic (DRD4), serotonergic (SLC64A), and GABA- ergic (GABRA2) neurotransmission, plus an array of Ancestry Informative Markers (AIMs) to identify ethnic ancestry and correct for population substructure. Third, 44% of the prospective sample will be tested in a placebo-controlled alcohol challenge to identify genetic influences on individual differences in response to the effects of alcohol. {Finally, we will assess mechanisms of genetic risk within a sophisticated structural equation modeling framework for longitudinal, multivariate data.} Thus, the proposed project will integrate 6 years of prospective behavioral data with new genotypying data and laboratory-assessed alcohol response endophenotypes. Results from the proposed project will facilitate early identification of individuals at high risk for developing an AUD and will contribute to the ultimate goal of developing more personalized targets of intervention.

Public Health Relevance

Young adults are at heightened risk for heavy alcohol use and alcohol use disorders (AUDs), which peak between 18 and 25 years. The proposed study will examine the impact of specific genes on patterns of heavy drinking during these critical years. The study also seeks to identify distinct behavioral mechanisms (alcohol response and generalized deviance) through which genes influence heavy drinking. Results will aid in tailoring intervention efforts to the specific mechanisms of risk for each individual.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
4R01AA020637-05
Application #
9087085
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Noronha, Antonio
Project Start
2012-09-20
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Wilhite, Emily R; Mallard, Travis; Fromme, Kim (2018) A longitudinal event-level investigation of alcohol intoxication, alcohol-related blackouts, childhood sexual abuse, and sexual victimization among college students. Psychol Addict Behav 32:289-300
Mallard, Travis T; Ashenhurst, James R; Harden, K Paige et al. (2018) GABRA2, alcohol, and illicit drug use: An event-level model of genetic risk for polysubstance use. J Abnorm Psychol 127:190-201
Marino, Elise N; Fromme, Kim (2018) Alcohol-induced blackouts, subjective intoxication, and motivation to decrease drinking: Prospective examination of the transition out of college. Addict Behav 80:89-94
Ashenhurst, James R; Harden, K Paige; Mallard, Travis T et al. (2017) Developmentally Specific Associations Between CNR1 Genotype and Cannabis Use Across Emerging Adulthood. J Stud Alcohol Drugs 78:686-695
Wilhite, Emily R; Ashenhurst, James R; Marino, Elise N et al. (2017) Freshman year alcohol and marijuana use prospectively predict time to college graduation and subsequent adult roles and independence. J Am Coll Health 65:413-422
Ashenhurst, James R; Wilhite, Emily R; Harden, K Paige et al. (2017) Number of Sexual Partners and Relationship Status Are Associated With Unprotected Sex Across Emerging Adulthood. Arch Sex Behav 46:419-432
Marino, Elise N; Fromme, Kim (2016) Early Onset Drinking Predicts Greater Level But Not Growth of Alcohol-Induced Blackouts Beyond the Effect of Binge Drinking During Emerging Adulthood. Alcohol Clin Exp Res 40:599-605
Gates, Jonathan R; Corbin, William R; Fromme, Kim (2016) Emerging adult identity development, alcohol use, and alcohol-related problems during the transition out of college. Psychol Addict Behav 30:345-55
Martin-Storey, Alexa; Fromme, Kim (2016) Trajectories of dating violence: Differences by sexual minority status and gender. J Adolesc 49:28-37
Wetherill, Reagan R; Fromme, Kim (2016) Alcohol-Induced Blackouts: A Review of Recent Clinical Research with Practical Implications and Recommendations for Future Studies. Alcohol Clin Exp Res 40:922-35

Showing the most recent 10 out of 17 publications