# Pathway-level transcriptional causal mechanism of sleep disordered breathing

> **NIH NIH R21** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $132,047

## Abstract

ABSTRACT
Sleep disordered breathing (SDB) affects more than 20% of the older population and increases the risks of
multiple cardiometabolic diseases and mortality. Candidate gene and genome-wide association studies (GWASs)
have identified genes and pathways associated with SDB. However, the causality is not clear. Transcriptome-
wide Mendelian randomization (MR) studies have recently been conducted to elucidate molecular mechanisms
of complex diseases. However, the power is limited by the number of tested genes and tissues and small effects
of single genes. Building on our preliminary data, we hypothesize that pathway-level transcriptional MR will
have better power than single gene MR to identify causal molecular mechanisms for SDB. In this study, we will
leverage well-established canonical pathways and existing methods to calculate pathway expression scores, as
well as available transcriptomics and genomics data in population-based studies. We will address the following
specific aims: 1) To describe tissue-specific and cross-tissue pathway activities using pathway expression scores
and identify genetic associations for these scores by performing GWAS; 2) To identify causal associations
between pathway activities and SDB by performing MR using GWAS summary statistics of pathway expression
scores and SDB traits. Results of this study will advance our knowledge of the molecular basis of SDB, help
identify SDB biomarkers, and provide novel treatment targets. This study also will provide a new approach to
understand causal mechanisms for other complex diseases.

## Key facts

- **NIH application ID:** 10895554
- **Project number:** 5R21HL165324-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Heming Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $132,047
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10895554

## Citation

> US National Institutes of Health, RePORTER application 10895554, Pathway-level transcriptional causal mechanism of sleep disordered breathing (5R21HL165324-02). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10895554. Licensed CC0.

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