Environmental Moderators of Genetic Liability for Suicidal Thoughts and Behaviors in US Veterans: A Multi-Omics Approach

About This Grant

The overall goal of the proposed CDA-2 is for Dr. Fischer to obtain advanced training in various methods of psychiatric genomics (e.g., statistical genetics, epigenetics, transcriptomics) that he can use to supplement and strengthen his existing program of research, which examines environmental risk and protective factors for various psychiatric disorders and clinical problems, including suicidal thoughts and behaviors (STBs). This training will enable Dr. Fischer to systematically and comprehensively examine the biopsychosocial etiology of STBs, which will ultimately help to inform the treatment and prevention of STBs in U.S. Veterans. To accomplish this goal, Dr. Fischer will investigate how environmental (i.e., psychosocial) risk and protective factors interact with polygenic liability for STBs, along with how epigenetic processes are associated with STB phenotypes (i.e., suicidal ideation and suicide attempts). This project is innovative in that it will be one of the first to examine whether psychosocial risk and protective factors potentiate or mitigate polygenic risk for suicide in U.S. Veterans. It will also be, by far, the largest study to date on the epigenomics of STBs and the first to derive methylation risk scores for STBs. The proposed study will leverage cutting-edge statistical methods and state-of-the-art bioinformatics to provide novel insights into the complex etiology of STBs that will ultimately help inform efforts to reduce Veteran death by suicide. This CDA-2 grant will build on Dr. Fischer’s strong scientific background in Veteran mental health, psychiatric epidemiology, and environmental risk and protective factors, along with his ongoing experiences as a clinical psychologist, to provide him with crucial new knowledge and skills, which will support the generation of novel, multidisciplinary research. Through the proposed CDA-2, Dr. Fischer will develop the ability to: 1) generate polygenic risk scores; 2) conduct gene enrichment analyses and transcriptome-wide association studies (TWAS); 3) perform drug repurposing analyses; 4) conduct epigenome-wide association studies (EWAS); 5) derive methylation risk scores; and 6) leverage advanced machine learning approaches to evaluate multi-level predictive models. Dr. Fischer’s multidisciplinary mentorship team is composed of world-leading experts working within the VA Connecticut Healthcare System and Yale University. The high-quality research and collaborative environment present at these institutions will facilitate Dr. Fischer’s transition into an independent VA researcher and equip him with the tools needed to produce impactful, innovative research that advances the U.S. Department of Veterans Affairs top research and clinical goals: suicide prevention.