The role of post-zygotic mutations in auto-immune disease

This project aims to advance our understanding of how military exposures such as Agent Orange and burn pits influence the risk for rheumatic disease such as rheumatoid arthritis among United States Veterans. There is evidence from many cohort studies that a wide variety of military and occupational exposures create a long-term risk for a wide variety of chronic diseases such as sarcoma, lymphoma, chronic obstructive pulmonary disease, and rheumatoid arthritis. But this research has not taken full advantage of the most powerful data resource for studying Veterans’ health: the Million Veterans Program (MVP). This project will leverage the outstanding scale and depth of the MVP to create a comprehensive dataset focused on the diseases which the candidate is an expert in treating: rheumatic diseases. Beyond simply documenting associations, this project will evaluate one potential pathway by which exposures may lead to disease: DNA damage. The genetic sequencing performed in the MVP allows researchers to detect DNA mutations in the blood of Veterans. I will aggregate all the DNA mutations that are more common among Veterans with each exposure to create a signature or “barcode” that can indicate whether a Veteran’s DNA retains evidence of that exposure. I will then statistically test whether those DNA barcodes are the pathway that connects exposure to disease. The candidate’s career goal is to become an independent physician-scientist at the Veterans Health Administration focused on developing novel ways to diagnose and treat rheumatic disease among Veterans. In addition to the proposed project, the training activities outlines in the Career Plan and Mentoring Plan are crucial to this application and to the candidate’s progress toward independence. Combined with the direct mentorship of Drs. Adrianna Hung and Alexander Bick, the Tennessee Valley Health System Nashville VAMC represents an ideal environment for the proposed work and leverages the world-class strengths of the Veterans Affairs resources. The Hung and Bick labs have deep experience in the methods and datasets used in this proposal and are prepared to support the candidate throughout the entirety of the grant period. Overall, this VA CDA-2 proposal represents a set of innovative and timely scientific aims combined with a tractable career development plan that will meaningfully contribute to Veterans’ health and catalyze the candidate’s long-term career goal of developing into an independent physician-scientist. Project Number: 1IK2RD001082-01 | Fiscal Year: 2026 | NIH Institute/Center: Veterans Affairs (VA) | Principal Investigator: Robert Corty | Institution: VETERANS HEALTH ADMINISTRATION, NASHVILLE, TN | Activity Code: IK2 | Study Section: Special Emphasis Panel[ZRD1 IMMA-G (01)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11300828