Resolving the AUD Phenotype: Unique and Transdiagnostic Features and Genetic Heterogeneity

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K.220.7: PROJECT SUMMARY/ABSTRACT Training: The major objectives of the proposed K99/R00 Pathway to Independence Award are Dr. Ashley Watts’ training in alcohol research and the launching of her career as an independent scientist. As a postdoctoral research fellow in the Department of Psychological Sciences at the University of Missouri, Dr. Watts is well along the path to becoming a leading psychopathology researcher. Dr. Watts seeks training and mentoring during the K99 phase to narrow her focus to alcohol use and alcohol use disorder and gain more training in quantitative genetics and modeling. Training in AUD will emphasize on AUD nosology; modern models of addiction, including their key neurobehavioral mechanisms; and individual differences in alcohol consumption. She will attend conferences related to alcohol use/misuse, behavior genetics, and psychopathology. She will also attend behavioral and molecular genetics workshops that span from human to animal models, as well as a neuroscience workshop; each of these workshops provides hands-on training in quantitative genetic techniques. This training will greatly extend Dr. Watts’ foundational knowledge and skill set. Dr. Watts will dedicate a great deal of her time to the dissemination of findings from the proposed research through manuscript preparation and submission. The proposed mentor and co-mentor (Drs. Kenneth Sher and Andrew Heath), collaborators (Drs. Wendy Slutske, Douglas Steinley, and Phillip Wood), and consultants (Drs. John Crabbe, Arpana Agrawal, Kathleen Bucholz, Kristina Jackson, and David Watson) collectively provide expertise that is ideally suited to facilitate the successful completion of the proposed training and research activities. Furthermore, the University of Missouri is a world-class research institution with the resources necessary to facilitate successful completion of the training (K99) phase of the proposed project. K99 Phase: With supervision, Dr. Watts will conduct secondary data analysis on phenotypic and genetic heterogeneity within AUD. This work will be achieved using a combination of large-scale cross-sectional and longitudinal phenotypic and genetically informative data. She will receive training via mentorship, coursework, workshops, readings, and consultation. R00 Phase: Dr. Watts will ascertain features of AUD that are specific to alcohol use, rather than general to substance use, externalizing psychopathology, or psychopathology more broadly using phenotypic, behavior genetic, and molecular genetic analysis. Significance: Her work will ultimately target sources of heterogeneity within AUD, characterize specific AUD vulnerabilities, and inform future precision-medicine efforts, each of which are emphasized by NIAAA’s emphases on the improvement of AUD diagnosis and understanding its relations with other forms of psychopathology (NIAAA, 2017).