# GXI Interactions

> **NIH NIH U19** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2024 · $604,090

## Abstract

PROJECT SUMMARY/ABSTRACT
 By 2050, more than 2 billion people worldwide will be over the age of 65, with older adults outnumbering
children for the first time in recorded history. This predicted major demographic shift highlights the importance
of improving our understanding of factors that contribute to healthy brain aging. Currently, the biological bases
of brain aging are poorly understood. Brain aging (often focused on cognitive decline) is characterized by
numerous phenotypes that undoubtedly involve multiple environmental and genetic factors. Overtly
pathological brain aging is seen in major neurological diseases such as Alzheimer’s disease and related
dementias (ADRD); the prevalence of ADRD is expected to double every 20 years. On top of this existing
public health crisis, we are now experiencing a global pandemic that appears to negatively influence
neurological function. Growing evidence indicates that SARS-CoV-2 infection causes neurological
complications of short-term consequence including acute neuropathy, encephalopathy, anosmia, and
hypoxic/ischemic brain injury, and longer-term consequences including cognitive impairment and
neuropsychiatric disturbances.
 The interindividual variation in the neurobiological responses to SARS-CoV-2 is marked. As with most
complex phenotypes, causal determinants likely include both genetic and environmental factors. However, no
genetic epidemiological study has yet considered differential neurophenotypic response to infection. Thus,
delineating the genetic architecture of ADRD-relevant neurophenotypic responses to SARS-CoV-2 will offer
important biological insights, which in turn could provide strategies for fostering healthy brain aging in the
presence of future infectious challenges. Our project will assess the genetic basis of ADRD-relevant
endophenotypic response (across a two year period with three examinations) to SARS-CoV-2 infection in a set
of older (>60 years of age) adults from diverse populations (Amerindians from Argentina [ n=3000], US Native
Americans [n=250], Mexican Americans [n=500], Puerto Ricans [n=125], African Americans [n=125], and
Africans [n=300]) using whole genome sequence (WGS) data in a case/control design (75% post-infection
cases, 25% never infected controls). The data generated will enable estimating the importance of genetics in
disease response and the identification of key genes involved in the response. Our specific aims are to: 1)
detect genetic influences on endophenotypic responses to SARS-CoV-2 infection using WGS data through
testing for genotype×infection interaction in neurocognitive measures (neurocognitive measures, neuroimaging
measures, and blood-based biomarkers); 2) search for sequence variation in genes and gene pathways
influencing response to SARS-CoV-2 infection; and 3) test whether between-population variation in mean
responses to infection has a genetic component. This project represents the genetic component of a large,
integrated U19 applicat...

## Key facts

- **NIH application ID:** 10907435
- **Project number:** 5U19AG076581-02
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** John Blangero
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $604,090
- **Award type:** 5
- **Project period:** 2023-08-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10907435

## Citation

> US National Institutes of Health, RePORTER application 10907435, GXI Interactions (5U19AG076581-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10907435. Licensed CC0.

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