Melissa A. Munn-Chernoff, Ph.D. - US grants

DESCRIPTION (provided by applicant): Disordered eating characteristics are eating attitudes and behaviors that may lead to the development of more life-threatening illnesses, such as eating disorders. Often referred to as eating pathology, disordered eating characteristics and eating disorders result from a combination of genetic and environmental factors. Although eating pathology commonly co-occurs with alcohol use and particular personality traits, understanding genetic and environmental contributions to this relationship has not been closely examined. One specific candidate gene that may play a role in individual differences in certain personality traits, as well as vulnerability to alcohol use disorder and eating pathology, is the serotonin transporter gene (SLC6A4). Initial results are promising, suggesting associations between polymorphisms in this gene and eating pathology, but independent replications of these findings are needed. Moreover, polymorphisms in SLC6A4 have been hypothesized to explain relationships among eating pathology, alcohol use, and personality, yet no study has directly assessed this hypothesis. Using existing data, this study will conduct secondary analyses to 1) investigate genetic and environmental relationships among disordered eating, alcohol use, and personality, 2) utilize a dense polymorphism map to examine associations of disordered eating with multiple polymorphisms in SLC6A4, and 3) analyze the extent to which polymorphisms in SLC6A4 explain relationships among disordered eating, alcohol use, and certain personality traits. Adolescent and young adult female twins and their female non-twin siblings participating in the Colorado Center for Antisocial Drug Dependence will be included in these analyses. Initially, biometrical model fitting will be used to assess genetic and environmental influences on these characteristics at both the univariate and multivariate levels. In addition, state-of-the-art statistical packages will be used that allow for appropriate analyses of candidate genes, especially when taking into account multiple phenotypes. Specifically, this study will look at associations between multiple polymorphisms in SLC6A4 with disordered eating. To the extent that these polymoprhisms are related to disordered eating, they will be examined while also taking into account alcohol use and personality traits. Identifying biological markers (i.e., genes) of disordered eating and related behaviors will not only add significant information to existing knowledge about what contributes to relationships among these behaviors, but may also shed light on the role pharmacological treatments may have in modifying these symptoms. The importance of identifying relationships among multiple behavioral characteristics that may share similar risk factors early on could potentially prevent the emergence of more harmful behaviors.

PROJECT SUMMARY Candidate: I am an Assistant Professor in the Department of Psychiatry at the University of North Carolina at Chapel Hill (UNC-CH). My overarching career goal is to develop an independent NIH-funded program of research that explicates the etiology of comorbid alcohol involvement (AI) and eating disorder (ED) pathology using sophisticated and comprehensive statistical methodologies that incorporate both genetic and environmental risk. I seek additional instruction in: (1) advanced training in ED and alcohol phenotypes; (2) adolescent development; and (3) modern genomic analyses. Research Project: Existing data from the Child and Adolescent Twin Study in Sweden (CATSS) will be leveraged with existing genome-wide association study (GWAS) data from the Psychiatric Genomics Consortium (PGC) to explore the manner and extent to which the comorbidity between AI and ED pathology are accounted for by genetic and environmental factors. Specific aims are to: (1) obtain descriptive information and explore genetic and environmental effects on comorbid AI and ED pathology in adolescence and young adulthood, and investigate the extent to which childhood adversity affects this association; (2) identify shared genetic risk factors for AI and ED pathology; and (3) develop and apply polygenic risk scores for AI and ED pathology to more comprehensively examine the genetic etiology of these behaviors. This research will provide crucial information to explicate the comorbidity between AI and ED pathology, as well as ultimately assist in developing targeted prevention strategies and enhance early detection and tailored interventions for these debilitating behaviors. Environment: The research and training will occur primarily at UNC-CH and secondarily at Washington University in St. Louis, MO (Department of Psychiatry). Training at both institutions is essential in order to work with the statisticians who are at the forefront of applying the methods proposed here to both AI and ED pathology. Mentors and Collaborators/Consultants: The mentorship team includes primary mentor, Dr. Cynthia Bulik, a clinical adolescent psychologist, internationally recognized ED specialist, and co-chair of the PGC-Eating Disorders working group; and co-mentor, Dr. Arpana Agrawal, a genetic and psychiatric epidemiologist, internationally recognized alcohol and substance use specialist, and co-chair of the PGC-Substance Use Disorders working group. Collaborators/consultants are: Dr. Andrea Hussong (developmental psychologist specializing in substance use and developmental trajectories); Dr. Paul Lichtenstein (genetic epidemiologist and CATSS PI); Dr. Kari North (genetic epidemiologist specializing in GWAS); and Dr. Benjamin Neale (statistical geneticist specializing in novel genomic analyses).