# Novel approaches for relating genetic variation in endogenous retroviruses to function and disease

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $254,250

## Abstract

PROJECT SUMMARY/ABSTRACT
Genome-wide association studies (GWAS) for complex traits have often revealed a significant proportion of risk
attributed to the non-coding genome. This has led our group to question whether single nucleotide
polymorphisms (SNPs) conferring disease risk, could be affecting the function of genetic elements which are
commonly excluded from omic studies, and whose functional role is largely unknown. Human endogenous
retroviruses (HERVs) are often found in the non-coding and intergenic regions of the genome, and due to their
incomplete annotation and repetitive nature, have been largely overlooked in both genomic and transcriptomic
analyses. This project utilizes a novel annotation, developed by our team, of 14,968 HERVs that contain internal
regions (which are therefore, more likely to generate functional transcripts), to better understand their role in
relation to 20 polygenic disease traits. First, we will integrate our HERV annotation with GWAS summary
statistics via gene level enrichment analyses, which will allow us to prioritize HERVs of etiological importance.
Second, we will perform HERV quantification in 51 tissues using our recently developed bioinformatic tool,
“Telescope”, which quantifies HERVs with single-locus specificity using RNA-seq data. Tissue-specific
expression quantitative trait loci (eQTL) and transcriptome-wide association studies (TWAS) will then be used to
assess the effect disease risk SNPs have on expression profiles in each tissue, and to prioritize risk-associated
HERVs for each trait on a whole-genome level, respectively. The intersection between HERVs implicated in the
etiology of each disease, and those functionally affected by cis-eQTL risk SNPs will aid in identifying biological
mechanisms pertaining to HERVs in disease risk, which may ultimately lead to new biomarkers or treatment
targets.

## Key facts

- **NIH application ID:** 10108518
- **Project number:** 1R21HG011513-01
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** DOUGLAS F NIXON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $254,250
- **Award type:** 1
- **Project period:** 2021-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108518

## Citation

> US National Institutes of Health, RePORTER application 10108518, Novel approaches for relating genetic variation in endogenous retroviruses to function and disease (1R21HG011513-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10108518. Licensed CC0.

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