Pathways to Alcohol Use Disorders in ALSPAC: A Genetic-Developmental Study Alcohol Use Disorders (AUDs) emerge from diverse genetic and environmental risk factors acting through a range of complex developmental pathways. Very few studies exist that have a combination of sample size, representativeness, and sufficiently frequent and detailed assessments over the requisite age range to provide a realistic opportunity to disentangle these intricate etiologic pathways. The Avon Longitudinal Study of Parents and Children (ALSPAC) is such a study. Beginning with over 13,000 pregnant mothers ascertained around Avon England, the ALSPAC project has conducted detailed follow-ups of this sample for the last 16 years. The sample is now entering the critical transitional period from adolescence to young adulthood. This application, prepared by a team of investigators from Virginia Commonwealth University and University of Bristol, has three specific aims in the ALSPAC cohort.
The first aim i s to add detailed assessments of alcohol use and symptoms of AUDs to questionnaires already scheduled to occur at ages 18 and 20. This will allow us to capture a key developmental phase for alcohol use and the emergence of early symptoms of AUDs.
The second aim i s to conduct an extensive series of analyses seeking to understand the etiologic pathways to alcohol use (AU) and alcohol use problems (AUPs). The specific goals of these analyses will be (1) to characterize patterns of AU and AUPs across adolescence;(2) to identify childhood risk factors that predict AU and AUPs in adolescence and to understand the developmental processes by which these risks unfold;(3) to study the further development of these risk factors across adolescence and their interaction with emerging AU and its consequences;(4) to test the moderating role of gender on patterns, predictors, and developmental processes related to AU and AUPs;and (5) to extend models of risk for AU and AUPs into young adulthood using the age 18 and 20 data collected under Aim 1. The analyses will examine how risk unfolds across development across three major domains: Externalizing, Internalizing, and Environment (and how these eventually relate to AU and the development of AUPs). Each of these domains is broad, and one of the goals of the project will be to parse these constructs and delineate the most relevant risk dimensions.
The third aim of the project is to incorporate information about a limited set of previously validated risk genes into developmental models of risk for AU, AUPs, and AUDs developed in Aim 2. This will be accomplished using molecular genetic data available on at least 3,000 subjects from the ALSPAC cohort at no cost to NIH. These analyses will allow us to study the dynamic interplay of biological, psychological, and social processes that contribute to pathways of risk (and resiliency) for AU and AUPs. With its large sample size, representativeness, detailed and frequent phenotypic assessments and availability of genotypic data, the ALSPAC cohort provides a unique opportunity to clarify, in a developmental context, the complex web of susceptibility and protective factors for AUDs.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA018333-03
Application #
8319651
Study Section
Behavioral Genetics and Epidemiology Study Section (BGES)
Program Officer
Scott, Marcia S
Project Start
2010-09-10
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$526,837
Indirect Cost
$145,595
Name
Virginia Commonwealth University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
105300446
City
Richmond
State
VA
Country
United States
Zip Code
23298
Edwards, Alexis C; Deak, Joseph D; Gizer, Ian R et al. (2018) Meta-Analysis of Genetic Influences on Initial Alcohol Sensitivity. Alcohol Clin Exp Res 42:2349-2359
Savage, Jeanne E; Salvatore, Jessica E; Aliev, Fazil et al. (2018) Polygenic Risk Score Prediction of Alcohol Dependence Symptoms Across Population-Based and Clinically Ascertained Samples. Alcohol Clin Exp Res 42:520-530
Mahedy, Liam; MacArthur, Georgina J; Hammerton, Gemma et al. (2018) The effect of parental drinking on alcohol use in young adults: the mediating role of parental monitoring and peer deviance. Addiction 113:2041-2050
Kendler, Kenneth S; Gardner, Charles O; Edwards, Alexis C et al. (2018) Childhood Risk Factors for Heavy Episodic Alcohol Use and Alcohol Problems in Late Adolescence: A Marginal Structural Model Analysis. J Stud Alcohol Drugs 79:370-379
Hammerton, Gemma; Mahedy, Liam; Murray, Joseph et al. (2017) Effects of Excessive Alcohol Use on Antisocial Behavior Across Adolescence and Early Adulthood. J Am Acad Child Adolesc Psychiatry 56:857-865
Edwards, Alexis C; Heron, Jon; Vladimirov, Vladimir et al. (2017) The Rate of Change in Alcohol Misuse Across Adolescence is Heritable. Alcohol Clin Exp Res 41:57-64
Cooke, Megan E; Neale, Zoe E; Barr, Peter B et al. (2017) The Role of Social, Familial, and Individual-Level Factors on Multiple Alcohol Use Outcomes During the First Year of University. Alcohol Clin Exp Res 41:1783-1793
Webb, Bradley T; Edwards, Alexis C; Wolen, Aaron R et al. (2017) Molecular Genetic Influences on Normative and Problematic Alcohol Use in a Population-Based Sample of College Students. Front Genet 8:30
Stapinski, Lexine A; Edwards, Alexis C; Hickman, Matthew et al. (2016) Drinking to Cope: a Latent Class Analysis of Coping Motives for Alcohol Use in a Large Cohort of Adolescents. Prev Sci 17:584-94
Wright, Michelle L; Dozmorov, Mikhail G; Wolen, Aaron R et al. (2016) Establishing an analytic pipeline for genome-wide DNA methylation. Clin Epigenetics 8:45

Showing the most recent 10 out of 32 publications