Alcoholism (alcohol abuse and dependence) is a common disorder with a peak age of onset in early adulthood and a complex etiology. Twin studies comprised predominantly of participants of European Caucasian ancestry have shown genetic factors contribute 40-60 percent of the risk for the development of alcohol dependence in both sexes. Yet, very little is currently known about how genetic influences on alcoholism are mediated or moderated (e.g., gene-environment interactions). The aldehyde dehydrogenase ALDH2 gene, to date, has the strongest and most consistent associations with alcohol dependence. The variant ALDH2*2 allele is found in high prevalence, and almost exclusively, in Asian populations. Using a sample of 18-19 year-old Chinese and Korean American college students, the proposed study aims to prospectively test key elements of a mechanistic pathway hypothesized to explain how possession of ALDH2*2 alleles protect individuals against alcohol use disorders (AUDs). It is hypothesized ALDH2*2 will lead to heightened responses to alcohol, reduced positive expectancies about alcohol, and decreased rates of use, heavy use, and adverse drinking consequences. The proposed study also aims to test for potential moderators of the relationships between ALDH2*2 and alcohol involvement variables. It is hypothesized that being female, Korean, highly acculturated, highly religious, highly antisocial, highly behaviorally undercontrolled, with greater negative affect, with a family history of AUDs, with parents who drink more heavily, with siblings who drink more heavily, with peers who drink more heavily, and without ADH1B*2 alleles will decrease the effect sizes of ALDH2*2. An exploratory aim of the proposed study is to examine other ADH and ALDH gene polymorphisms for associations with alcohol involvement variables. Findings from this research will provide important information about the developmental course of alcohol use and alcohol problems in an understudied population, Asian American men and women, during a period of high environmental risk for drinking behavior (college attendance). The identification of gene modifiers using explicitly measured variables will provide a more comprehensive understanding of the complex interplay of factors and processes involved in the etiology of alcohol involvement.

Public Health Relevance

Results from this study will contribute to a more comprehensive understanding of the causal relationship between the ALDH2 gene and the progression of alcohol-related behaviors, as well as the complex interplay of factors and processes involved in the etiology of alcohol involvement. Insofar as much remains to be learned about the etiology of alcoholism in the general population, these findings will contribute to a greater understanding of racial and ethnic disparities in the causes and consequences of alcohol involvement and the generalizability of findings across groups. Through this understanding, findings from the proposed research have the potential to lead to more effective prevention of alcoholism.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA011257-11A2
Application #
7584716
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Matochik, John A
Project Start
2009-09-10
Project End
2011-08-31
Budget Start
2009-09-10
Budget End
2010-08-31
Support Year
11
Fiscal Year
2009
Total Cost
$640,040
Indirect Cost
Name
Veterans Medical Research Fdn/San Diego
Department
Type
DUNS #
933863508
City
San Diego
State
CA
Country
United States
Zip Code
92161
Luk, Jeremy W; Liang, Tiebing; Wall, Tamara L (2017) Gene-by-Environment Interactions on Alcohol Use Among Asian American College Freshmen. J Stud Alcohol Drugs 78:531-539
Luczak, Susan E; Liang, Tiebing; Wall, Tamara L (2017) Age of Drinking Initiation as a Risk Factor for Alcohol Use Disorder Symptoms is Moderated by ALDH2*2 and Ethnicity. Alcohol Clin Exp Res 41:1738-1744
Luczak, Susan E; Wall, Tamara L (2016) Gambling problems and comorbidity with alcohol use disorders in Chinese-, Korean-, and White-American college students. Am J Addict 25:195-202
Qiu, Bin; Luczak, Susan E; Wall, Tamara L et al. (2016) The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans. Int J Mol Sci 17:
Luczak, Susan E; Rosen, I Gary; Wall, Tamara L (2015) Development of a real-time repeated-measures assessment protocol to capture change over the course of a drinking episode. Alcohol Alcohol 50:180-7
Luczak, Susan E; Yarnell, Lisa M; Prescott, Carol A et al. (2014) Effects of ALDH2?2 on alcohol problem trajectories of Asian American college students. J Abnorm Psychol 123:130-40
Chartier, Karen G; Scott, Denise M; Wall, Tamara L et al. (2014) Framing ethnic variations in alcohol outcomes from biological pathways to neighborhood context. Alcohol Clin Exp Res 38:611-8
Otto, Jacqueline M; Hendershot, Christian S; Collins, Susan E et al. (2013) Association of the ALDH1A1*2 promoter polymorphism with alcohol phenotypes in young adults with or without ALDH2*2. Alcohol Clin Exp Res 37:164-9
Luczak, Susan E; Pandika, Danielle; Shea, Shoshana H et al. (2011) ALDH2 and ADH1B interactions in retrospective reports of low-dose reactions and initial sensitivity to alcohol in Asian American college students. Alcohol Clin Exp Res 35:1238-45
Duranceaux, Nicole C E; Schuckit, Marc A; Luczak, Susan E et al. (2008) Ethnic differences in level of response to alcohol between Chinese Americans and Korean Americans. J Stud Alcohol Drugs 69:227-34

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