Candidate: I am NIH T32 Postdoctoral Fellow with the UNC Center of Excellence for Eating Disorders in the Department of Psychiatry at the University of North Carolina (UNC) at Chapel Hill. Career Goals: My ultimate goal is to develop sophisticated risk prediction models for eating disorders and empirically related phenotypes in a transdiagnostic manner. Gene-environment integration through modern genomic techniques and measured epidemiological data will yield important information for improved understanding of etiology, enhanced detection and diagnosis, and eventually individually targeted therapeutics. Career Development: My expertise is in neurogenetics, and I need additional mentored training to build my skills in three areas: (1) statistical genetics and GWAS; (2) bioinformatics; and (3) genetic epidemiology. Research Project: This study leverages existing resources by using data from Danish national registers and genotypes funded by ongoing projects. First, I will identify shared and unique genetic risk factors for anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) by conducting disorder-specific and cross-disorder GWAS in 5,300 AN and 6,500 OCD cases from Denmark. I will then examine their genetic correlation and co- heritability to assess how their genetic architectures relate to each other and to other phenotypes. Second, I will develop a Polygenic Risk Score (PRS) for genetic liability to AN and shared AN-OCD risk. Using Danish national register data, I will develop risk equations that combine genetic and environmental factors for AN-OCD prediction. Third, I will study AN cases with extreme PRS (i.e., top and bottom deciles) to determine whether differences exist in their cumulative environmental risk burden or specific risk factors. In future independent applications (R01s), these results will inform further explorations on mapping unique contributions of genes and environment to predict eating disorder risk and developing multifactorial predictive models. Environment: The majority of the research and training will take place in the Departments of Psychiatry and Genetics at UNC. I will also receive training in genetic epidemiology at Aarhus University in Denmark. Mentorship: The core mentorship team consists of Dr. Cynthia Bulik, lead mentor, who is an internationally recognized expert in eating disorder research, and Dr. James Crowley, co-lead mentor, a psychiatric geneticist who has built a collaborative network of OCD research in Scandinavia. Dr. Manuel Mattheisen, co-mentor, has extensive experience in gene-environmental risk modeling. Dr. Jin Szatkiewicz, co-mentor, is experienced in developing statistical and computation methods to test genetic hypotheses. Dr. Preben Bo Mortensen, collaborator, is a specialist in register-based psychiatric epidemiology. Dr. Patrick Sullivan, consultant, is a leading expert in psychiatric genetics. Dr. Judith Nissen, consultant, is a skilled clinician specializing in OCD. Their combined mentorship will place me in an ideal position to succeed as an independent investigator.

Public Health Relevance

Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are serious psychiatric disorders with biological basis and carry unacceptably high personal, familial, and societal costs. AN and OCD are notably comorbid with each other, share similar core symptoms, and co-exist in families, suggesting the presence of shared risk factors contributing to their development. Considering our limited knowledge about the causes of AN and OCD, examining the shared genetic and epidemiological risk factors and developing sophisticated risk prediction models could ultimately assist in early detection, differential diagnosis, and personalized treatment options for these devastating disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01MH109782-01
Application #
9088554
Study Section
Genetics of Health and Disease Study Section (GHD)
Program Officer
Van'T Veer, Ashlee V
Project Start
2016-04-01
Project End
2020-03-31
Budget Start
2016-04-01
Budget End
2017-03-31
Support Year
1
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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