# Next Generation Rare Variant Discovery in Multiplex AD Families

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2020 · $156,267

## Abstract

The World Health Organization (WHO) is currently reporting 4,793,076 confirmed cases of
COVID-19 infection world-wide with 316,341 deaths. With each new pandemic the population is at
risk until vaccines and medications can be developed. Quarantine of the entire population appears
to be only alternative until sufficient time elapses for vaccine development. Therefore, an
important public health goal is to determine who must be sheltered in place and who can resume
normal activities. Older individuals appear to be disproportionately adversely affected by the
virus. Although immune functioning tends to wane with age, genetic and lifestyle factors appear to
greatly alter susceptibility. The goal of this project is to identify individuals who may be more or
less resilient due to their lifetime use of alcohol. Those with an alcohol use disorder (AUD) may
have a greater risk for adverse consequences of SARS-CoV-2 exposure, yet low dose
consumption may improve immune functioning. A better understanding of whether alcohol use has
a different effect at low doses than at high doses is critical to public health campaigns that advise
the public on safe use of alcohol. Genetic variation in the Major Histocompatiblity Locus (MHC)
located on chromosome 6 plays an important role in immune functioning. Variation in the human
leucocyte antigens (HLA) have been significantly associated with many diseases and hold promise
for personalized antigen-specific disease prevention. Having this information available, as part of
routine medical screening in the future, would enable us to stratify the population into those
needing sheltering in place and those who do not. This project would determine the feasibility of
using HLA gene variation along with screening for alcohol use as an important part of stratifying
the population at the onset of viral epidemics.
 The present proposal builds on existing resources from participants for whom exome
sequencing and/or HLA serology was completed and utilizes the extensive alcohol use histories,
psychiatric diagnoses, and health histories obtained at baseline. New interviews concerning
alcohol use, both distal and proximal, current health status, and exposure histories for the SARS-
CoV-2 virus will enable us to determine their contribution to infection and progression. We will
contrast those with AUD with those without and unaffected members of high risk versus low risk
families in (Aim 1). In Aim 2, we will assess levels of recent and past alcohol consumption to viral
response. Genetic variation in the major histocompatibility complex (HLA) region will be tested for
association with outcome among those that are demonstrated to have been exposed (Aim 3).

## Key facts

- **NIH application ID:** 10214751
- **Project number:** 3R01AA021746-05S1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** David B. Goldstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $156,267
- **Award type:** 3
- **Project period:** 2015-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10214751

## Citation

> US National Institutes of Health, RePORTER application 10214751, Next Generation Rare Variant Discovery in Multiplex AD Families (3R01AA021746-05S1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10214751. Licensed CC0.

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