# Using GTEx to assess the functionality of sex-biased variants

> **NIH NIH R03** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $121,896

## Abstract

Contact PD/PI: Soemedi, Rachel
PROJECT SUMMARY
Sex differences in human diseases are well-recognized, but the mechanisms are not well
understood. This gap of knowledge delays the progress in risk assessment and therapeutic
strategies for sex-aware precision healthcare. While studies have shown significant sex
differences in the genetic architectures of complex diseases, most investigators opted to do sex-
combined analyses in disease genetic studies to maximize statistical power. NIH recently began
to reinforce the inclusion of sex as a biological variable in the design, analysis, and reporting of
vertebrate animal and human studies. Insights into the functional genetic bases of sex as a
biological variable are critical to develop therapeutic interventions that equally benefit each sex.
We recently found that ~1% variants in the population have sex-biased allele frequency, including
~10% of disease variants in the Genome Aggregation Database (gnomAD). These variants
preferentially occur in tissue-specific sex-differentially expressed genes. We propose a novel
approach to study sex differences in disease genetic architectures by leveraging variants that are
sex-biased either in allele frequency or phenotypic association. We believe this approach will
increase the statistical power to identify sex-specific or sex interacting causal variants in sex-
biased diseases. We will identify and characterize sex-biased variants in gnomAD, Genotype-
Tissue Expression project (GTEx) and Trans-Omics for Precision Medicine for sleep disordered
breathing phenotypes and venous thromboembolism case-control datasets. We will subsequently
study the functional mechanisms of these sex-biased variants in ~50 GTEx tissues. The
completion of this pilot study will advance future genetic studies of sex-divergent disorders and
accelerate the realization of sex-aware genomic medicine.
Project Summary/Abstract Page 6

## Key facts

- **NIH application ID:** 10435681
- **Project number:** 7R03OD030598-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Rachel Soemedi
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $121,896
- **Award type:** 7
- **Project period:** 2021-07-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435681

## Citation

> US National Institutes of Health, RePORTER application 10435681, Using GTEx to assess the functionality of sex-biased variants (7R03OD030598-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10435681. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*