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Radhakrishnan K, Hauser ER, Polimanti R, et al. Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990-1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006. Brain Sci. 2021;11(7)doi: 10.3390/brainsci11070845.
Radhakrishnan, K., Hauser, E. R., Polimanti, R., Helmer, D. A., Provenzale, D., McNeil, R. B., Maffucci, A., Quaden, R., Zhao, H., Whitbourne, S. B., Harrington, K. M., Vahey, J., Gelernter, J., Levey, D. F., Huang, G. D., Gaziano, J. M., Concato, J., & Aslan, M. (2021). Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990-1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006. Brain sciences, 11(7), . https://doi.org/10.3390/brainsci11070845
Radhakrishnan, Krishnan, et al. "Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990-1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006." Brain sciences vol. 11,7 (2021). doi: https://doi.org/10.3390/brainsci11070845
Radhakrishnan K, Hauser ER, Polimanti R, Helmer DA, Provenzale D, McNeil RB, Maffucci A, Quaden R, Zhao H, Whitbourne SB, Harrington KM, Vahey J, Gelernter J, Levey DF, Huang GD, Gaziano JM, Concato J, Aslan M. Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990-1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006. Brain Sci. 2021 Jun 25;11(7). doi: 10.3390/brainsci11070845. PMID: 34202057; PMCID: PMC8301942.
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Brain Sci. 2021 Jun 25;11(7). doi: 10.3390/brainsci11070845.

Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990-1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006.

Brain sciences

Krishnan Radhakrishnan, Elizabeth R Hauser, Renato Polimanti, Drew A Helmer, Dawn Provenzale, Rebecca B McNeil, Alysia Maffucci, Rachel Quaden, Hongyu Zhao, Stacey B Whitbourne, Kelly M Harrington, Jacqueline Vahey, Joel Gelernter, Daniel F Levey, Grant D Huang, John Michael Gaziano, John Concato, Mihaela Aslan

Affiliations

  1. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, Rockville, MD 20857, USA.
  2. College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
  3. VA Cooperative Studies Program Epidemiology Center-Durham, Department of Veterans Affairs, Durham, NC 27705, USA.
  4. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27705, USA.
  5. Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA Connecticut Healthcare System, West Haven, CT 06516, USA.
  6. School of Medicine, Yale University, New Haven, CT 06511, USA.
  7. Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA.
  8. Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
  9. Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA 02130, USA.
  10. Department of Biostatistics, Yale School of Public Health, New Haven, CT 06520, USA.
  11. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  12. Department of Medicine, Division of Aging, Brigham and Women's Hospital, Boston, MA 02115, USA.
  13. Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118, USA.
  14. Computational Biology and Bioinformatics Program, Duke University, Durham, NC 27705, USA.
  15. Division of Human Genetics, Department of Psychiatry, School of Medicine, Yale University, New Haven, CT 06511, USA.
  16. Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT 06516, USA.
  17. Cooperative Studies Program, VA Office of Research and Development, Washington, DC 20420, USA.
  18. Food and Drug Administration, Silver Spring, MD 20993, USA.

PMID: 34202057 PMCID: PMC8301942 DOI: 10.3390/brainsci11070845

Abstract

BACKGROUND: Approximately 697,000 members of the U.S. Armed Forces were deployed to the Persian Gulf in support of the 1990-1991 Persian Gulf War (GW). Subsequently, many deployed and some non-deployed veterans developed a chronic multi-symptom illness, now named Gulf War Illness (GWI). This manuscript outlines the methods and rationale for studying the genomics of GWI within the Million Veteran Program (MVP), a VA-based national research program that has linked medical records, surveys, and genomic data, enabling genome-wide association studies (GWASs).

METHODS: MVP participants who served in the military during the GW era were contacted by mail and invited to participate in the GWI study. A structured health questionnaire, based on a previously tested instrument, was also included in the mailing. Data on deployment locations and exposures, symptoms associated with GWI, clinical diagnoses, personal habits, and health care utilization were collected. Self-reported data will be augmented with chart reviews and structured international classification of disease codes, to classify participants by GWI case status. We will develop a phenotyping algorithm, based on two commonly used case definitions, to determine GWI status, and then conduct a nested case-control GWAS. Genetic variants associated with GWI will be investigated, and gene-gene and gene-environment interactions studied. The genetic overlap of GWI with, and causative mechanisms linking this illness to, other health conditions and the effects of genomic regulatory mechanisms on GWI risk will also be explored.

CONCLUSIONS: The proposed initial GWAS described in this report will investigate the genomic underpinnings of GWI with a large sample size and state-of-the-art genomic analyses and phenotyping. The data generated will provide a rich and expansive foundation on which to build additional analyses.

Keywords: Gulf War Illness; Persian Gulf War deployment status; U.S. veteran; exposures; genomics; phenotyping

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