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.

Agency
National Institute of Health (NIH)
Type
Research Scientist Award (K05)
Project #
5K05AA017688-07
Application #
8726889
Study Section
Biomedical Research Review Subcommittee (AA)
Program Officer
Scott, Marcia S
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Sartor, Carolyn E; Grant, Julia D; Duncan, Alexis E et al. (2016) Childhood sexual abuse and two stages of cigarette smoking in African-American and European-American young women. Addict Behav 60:131-6
Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun et al. (2016) Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts. Behav Genet 46:151-69
Werner, K B; McCutcheon, V V; Challa, M et al. (2016) The association between childhood maltreatment, psychopathology, and adult sexual victimization in men and women: results from three independent samples. Psychol Med 46:563-73
Agrawal, Arpana; Few, Lauren; Nelson, Elliot C et al. (2016) Adolescent cannabis use and repeated voluntary unprotected sex in women. Addiction 111:2012-2020
Werner, Kimberly B; Grant, Julia D; McCutcheon, Vivia V et al. (2016) Differences in childhood physical abuse reporting and the association between CPA and alcohol use disorder in European American and African American women. Psychol Addict Behav 30:423-33
Kristjansson, Sean; McCutcheon, Vivia V; Agrawal, Arpana et al. (2016) The variance shared across forms of childhood trauma is strongly associated with liability for psychiatric and substance use disorders. Brain Behav 6:e00432
Trela, Constantine J; Piasecki, Thomas M; Bartholow, Bruce D et al. (2016) The natural expression of individual differences in self-reported level of response to alcohol during ecologically assessed drinking episodes. Psychopharmacology (Berl) 233:2185-95
Knopik, Valerie S; Marceau, Kristine; Palmer, Rohan H C et al. (2016) Maternal Smoking During Pregnancy and Offspring Birth Weight: A Genetically-Informed Approach Comparing Multiple Raters. Behav Genet 46:353-64
Knopik, Valerie S; Marceau, Kristine; Bidwell, L Cinnamon et al. (2016) Smoking during pregnancy and ADHD risk: A genetically informed, multiple-rater approach. Am J Med Genet B Neuropsychiatr Genet 171:971-81
Werner, K B; McCutcheon, V V; Agrawal, A et al. (2016) The association of specific traumatic experiences with cannabis initiation and transition to problem use: Differences between African-American and European-American women. Drug Alcohol Depend 162:162-9

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