This K05 competing renewal application seeks continued support for the applicant's research and junior faculty mentoring program, which investigates gene-environment interplay in alcohol use disorder onset, course and consequences, with a particular emphasis on understanding female AUD. The candidate has been continuously funded by NIAAA as R01 PI since 1988, and has over 500 publications, many highly cited. He has led many investigations on the genetic epidemiology of alcohol use disorder. His career development plan seeks to acquire knowledge to further expand the reach of his research, to take advantage of emerging opportunities in whole genome sequencing (for gene discovery using his Australian twin-family series), metagenomics (including its potential for biomarker development), spatial epidemiology (to allow merging of ecological data on neighborhood alcohol-related risk-factors with existing cohort studies), and neuroimaging (to maximize the value for the alcohol research community of his role in the Human Connectome Project): in other words, seeks to continue to improve characterization of genetic (perhaps including metagenomic) risks, characterization of environmental risks, and phenotyping, to further gene-environment interplay understanding, taking advantage of the unique institutional environment for these areas of research. He will mentor 3-5 junior faculty with research focused on varied aspects of AUD risk: e.g. (i) predictors of remission in women with severe alcoholism;(ii) childhood sexual abuse effects on alcohol use patterning;(iii) statistical modeling to detect excessive drinking effects on human brain functional connectivity;(iv) maternal alcoholism, parental separation, and early-onset drinking;(v) processes underlying alcoholism-binge eating comorbidity. His research plan focuses on two priority areas - extension of his follow-up of the MOAFTS twin cohort, to focus on predictors of remission of alcohol problems;and high-risk research using fecal sample collection from current and former excessive drinkers and BMI-matched controls, combined with bacterial 16S rRNA gene sequencing, to determine whether chronic alcohol effects on gut microbial ecology can lead to new approaches for the detection of excessive drinking.

Public Health Relevance

Though more prevalent in males, alcoholism represents an important public health problem in women as well, often with serious medical and social consequences. The applicant's goal is to improve understanding of the etiology, course and consequences of female alcohol use disorder, through research and junior faculty mentoring, with immediate goals of improving characterization of the factors predicting successful remission of alcohol problems, and developing improved methods for detecting excessive drinking.

National Institute of Health (NIH)
Research Scientist Award (K05)
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Biomedical Research Review Subcommittee (AA)
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Scott, Marcia S
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Washington University
Schools of Medicine
Saint Louis
United States
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Munn-Chernoff, Melissa A; Grant, Julia D; Agrawal, Arpana et al. (2015) Are there common familial influences for major depressive disorder and an overeating-binge eating dimension in both European American and African American female twins? Int J Eat Disord 48:375-82
Loukola, A; Wedenoja, J; Keskitalo-Vuokko, K et al. (2014) Genome-wide association study on detailed profiles of smoking behavior and nicotine dependence in a twin sample. Mol Psychiatry 19:615-24
Agrawal, Arpana; Madden, Pamela A F; Bucholz, Kathleen K et al. (2014) Initial reactions to tobacco and cannabis smoking: a twin study. Addiction 109:663-71
Koren, Rachel; Duncan, Alexis E; Munn-Chernoff, Melissa A et al. (2014) Preliminary evidence for the role of HTR2A variants in binge eating in young women. Psychiatr Genet 24:28-33
Pergadia, Michele L; Der-Avakian, Andre; D'Souza, Manoranjan S et al. (2014) Association between nicotine withdrawal and reward responsiveness in humans and rats. JAMA Psychiatry 71:1238-45
Heath, Andrew C; Waldron, Mary C; Martin, Nicholas G et al. (2014) Human mate selection and addiction: a conceptual critique. Behav Genet 44:419-26
van den Berg, St├ęphanie M; de Moor, Marleen H M; McGue, Matt et al. (2014) Harmonization of Neuroticism and Extraversion phenotypes across inventories and cohorts in the Genetics of Personality Consortium: an application of Item Response Theory. Behav Genet 44:295-313
Waldron, Mary; Vaughan, Ellen L; Bucholz, Kathleen K et al. (2014) Risks for early substance involvement associated with parental alcoholism and parental separation in an adolescent female cohort. Drug Alcohol Depend 138:130-6
Power, R A; Verweij, K J H; Zuhair, M et al. (2014) Genetic predisposition to schizophrenia associated with increased use of cannabis. Mol Psychiatry 19:1201-4
McCutcheon, Vivia V; Kramer, John R; Edenberg, Howard J et al. (2014) Social contexts of remission from DSM-5 alcohol use disorder in a high-risk sample. Alcohol Clin Exp Res 38:2015-23

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