Integrating Twin, Molecular, and Developmental Approaches to Understanding Alcohol Misuse: This application requests funding for a five year K02 award, with the overarching goal of developing an interdisciplinary program of research aimed at advancing our understanding of how genetic influences impact the development of alcohol use disorders. This will be accomplished by integrating findings across twin studies, gene identification projects, and longitudinal, community-based samples. The research plan has three broad aims: (1) To use twin studies to characterize the nature of genetic and environmental influences on alcohol use and related disorders, with focus on (a) studying the changing influence of genetic effects as a function of the environment and across development, and (b) understanding how genetic influences impact the phenotypic spectrum of risk associated with alcohol use disorders.
The second aim (2) is to identify genes involved in alcohol use and related phenotypes.
The third aim (3) is to characterize the risk associated with identified genes using community-based samples of individuals studied longitudinally, to test how the effect associated with specific genes may change across development and in conjunction with specific environmental factors.
These aims will be accomplished by integrating data across several of my funded projects: two population-based twin samples, FinnTwin12 and the Virginia Adult Twin Study of Psychiatric and Substance Use disorders;two gene identification projects: the Collaborative Study on the Genetics of Alcoholism and the Irish Affected Sib Pair Study of Alcohol Dependence;and three longitudinal, community-based samples: the Child Development Project, a study of ~500 children followed annually from age 5-25;the Mobile Youth Study, an on-going study of African-American children ages 10-18 from high-risk, impoverished neighborhoods;and the Avon Longitudinal Study of Parents and Children, an epidemiological cohort of ~10,000 children enrolled from a geographically-limited region in the UK, and assessed repeatedly (minimally yearly) prenatally through young adulthood. Accordingly, this project integrates findings across a number of research approaches, using results from twin studies about the nature of genetic influences (Aim 1) to develop hypotheses to test about the risk associated with specific genes (identified in Aim 2) in longitudinal, community samples (Aim 3). Together, these studies will synergize to advance our understanding of how genetic and environmental factors come together to influence to the development of alcohol problems. To inform my ability to conduct the proposed analyses, focused career development is proposed in two new content areas: (i) early childhood risk factors for alcohol problems, and (ii) racial differences in risk factors for alcohol problems, and two methodological areas: (i) GWAS methodology, and (ii) longitudinal data analyses. These stem directly from my funded projects and represent expansions to my current areas of expertise in alcohol research.
The complexity of the genetics of alcohol dependence necessitates a variety of research approaches. This project integrates analyses from twin studies, used to characterize the nature of genetic influences on alcohol- related phenotypes;molecular genetic studies, aimed at gene identification;and community-based samples, used to characterize the risk associated with specific genes across development and as a function of the environment. Understanding how genetic and environmental factors interact across development will be critical to develop more effective, tailored programs of prevention and intervention.
|Su, Jinni; Kuo, Sally I-Chun; Bucholz, Kathleen K et al. (2018) Understanding Mechanisms of Genetic Risk for Adolescent Internalizing and Externalizing Problems: The Mediating Role of Parenting and Personality. Twin Res Hum Genet 21:310-321|
|Aliev, Fazil; Salvatore, Jessica E; Agrawal, Arpana et al. (2018) A Brief Critique of the TATES Procedure. Behav Genet 48:155-167|
|Docherty, Anna R; Moscati, Arden; Dick, Danielle et al. (2018) Polygenic prediction of the phenome, across ancestry, in emerging adulthood. Psychol Med 48:1814-1823|
|Su, Jinni; Kuo, Sally I-Chun; Aliev, Fazil et al. (2018) Influence of Parental Alcohol Dependence Symptoms and Parenting on Adolescent Risky Drinking and Conduct Problems: A Family Systems Perspective. Alcohol Clin Exp Res 42:1783-1794|
|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|
|Salvatore, Jessica E; Dick, Danielle M (2018) Genetic influences on conduct disorder. Neurosci Biobehav Rev 91:91-101|
|Johnson, Emma C; Tillman, Rebecca; Aliev, Fazil et al. (2018) Exploring the relationship between polygenic risk for cannabis use, peer cannabis use, and the longitudinal course of cannabis involvement. Addiction :|
|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|
|Thomas, Nathaniel S; Adkins, Amy; Aliev, Fazil et al. (2018) Alcohol Metabolizing Polygenic Risk for Alcohol Consumption in European American College Students. J Stud Alcohol Drugs 79:627-634|
|Korhonen, Tellervo; Sihvola, Elina; Latvala, Antti et al. (2018) Early-onset tobacco use and suicide-related behavior - A prospective study from adolescence to young adulthood. Addict Behav 79:32-38|
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