# Host Genetic and Epigenetic Factors of the Progression, Comorbidities and Outcomes of Viral Infection

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2023 · —

## Abstract

Viral infections including Human immunodeficiency virus (HIV), hepatitis C virus (HCV)
and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have placed a substantial
strain on human health and the health care system. These infections have specifically had broad
impacts on veteran health in the US. Host factors influence how humans respond to infectious
agents and develop adverse health outcomes after infection. Although previous genome-wide
association studies (GWAS) have identified loci associated with susceptibility and progression for
several infections, understanding the role of host genetic and epigenetic factors on chronic
disease comorbidities, aging, and long-term outcomes in the setting of viral infections has been
hampered by sample size, heterogeneous populations, and discordant measurements/definitions
of key phenotypes. Recent epigenome-wide association studies (EWAS) have uncovered DNA
methylation markers associated with noncommunicable diseases (NCDs, such as coronary heart
disease, diabetes, heart failure, chronic kidney disease), as well as HIV infection. However, the
epigenetic predictors for incident NCDs and mortality are largely unknown among people with
viral infections. Viral infections (e.g., HIV) can have a substantial impact on epigenetics, which
may affect long-term health outcomes. Additionally, acceleration of the epigenetic clock or age
has emerged as a novel biomarker of biological aging and can predict disease outcomes and
mortality. Therefore, we will systematically investigate genetic and epigenetic predictors of NCDs
and mortality in the following Aims. 1) To identify genetic and epigenetic predictors of age-related
morbidity and mortality as well as modification effect of HIV infection among multi-ethnic veterans;
2) To identify genetic and epigenetic factors associated with morbidity and mortality among multi-
ethnic veterans with HCV infection; 3) To identify genetic and epigenetic factors of long-term
comorbidities, accelerated aging and mortality, as well as mediation effect of COVID-19 among
multi-ethnic veterans.
 Impact: Viral infections including HIV, HCV and SARS-CoV-2 broadly affects veteran’s
health and reduces the quality of life (healthspan) and life expectancy (lifespan) through a range
of comorbidities. The molecular mechanisms underlying the morbidity and mortality after viral
infections of HIV, HCV and SARS-CoV-2 are largely unknown. The proposed genetic and
epigenetic study can reveal the genetic and epigenetic factors linking viral infection (acute,
chronic, and resolved) and major NCD outcomes and mortality among multi-ethnic veterans, shed
lights on potential targets for new prevention and intervention, provide insights into the
comorbidity and aging process for all people, and develop systematic and precision medicine
strategies to improve veteran’s health.

## Key facts

- **NIH application ID:** 10485494
- **Project number:** 1I01BX006008-01
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** Vincent Charles Marconi
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2022-10-01 → 2026-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10485494

## Citation

> US National Institutes of Health, RePORTER application 10485494, Host Genetic and Epigenetic Factors of the Progression, Comorbidities and Outcomes of Viral Infection (1I01BX006008-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10485494. Licensed CC0.

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