# Elucidating Inflammatory and Metabolic Pathways in Obstructive Sleep Apnea Development

> **NIH NIH K01** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $177,068

## Abstract

ABSTRACT
Obstructive sleep apnea (OSA) is a common chronic sleep disorder in adults with a serious impact on health.
In addition to age and sex, obesity has been identified as the strongest risk factor for OSA. However, the
underlying mechanisms linking obesity with OSA pathogenesis are not fully understood. Although
accumulating evidence (based predominantly on cross-sectional studies) suggests that inflammation and
metabolic dysfunction may represent two potential modifiable etiologic pathways for OSA, few population-
based, prospective studies have been conducted to evaluate their roles in OSA development. In this highly
translational project, I will leverage the wealth of data from 4 large prospective US cohorts: the Nurses' Health
Study (NHS), NHSII, the Health Professional Follow-up Study (HPFS) and the Multi-Ethnic Study of
Atherosclerosis (MESA). I will use genetic and biomarker-based approaches to elucidate the importance of
inflammatory and metabolic pathways in OSA etiology. In Aim 1, I will use Mendelian randomization to
examine whether genetic susceptibility to obesity, inflammation and metabolic dysfunction is associated with
higher risk of developing OSA. Results from Mendelian randomization will help distinguish causal from non-
causal associations that arise from non-genetic, cross-sectional, observational studies due to confounding or
reverse causation. I will further examine gene-lifestyle interactions and sex differences in these genetic
associations. In Aim 2, I will evaluate whether inflammatory (e.g., CRP, IL-6, TNF-α) and metabolic (e.g.,
metabolomics, insulin, leptin, cholesterol) biomarkers that have been measured from archived blood samples
predict sleep-disordered breathing. These biomarkers will provide further insights into the mechanistic
pathways that may serve as potential therapeutic and pharmaceutical targets for intervention. Lastly, I will
measure sleep-disordered breathing in 200 NHS/NHSII/HPFS participants using an FDA-approved device
designed for at-home OSA diagnosis, and replicate the biomarker associations in Aim 2 with the objective
measures. I will acquire additional expertise in sleep epidemiology, OSA physiology, genetic analysis, and
primary sleep data collection/management. My training and research will be guided by a world-class
mentoring/consulting team, each with substantial expertise in the core areas: Drs. Susan Redline (OSA), Frank
Hu (lifestyles), Shelley Tworoger (biomarkers), Richa Saxena (genetics), Clary Clish (metabolomics) and Eric
Tchetgen Tchetgen (biostatistics). In sum, this innovative project will advance our understanding of the
inflammatory and metabolic pathways in OSA development from multiple dimensions, and help me emerge as
an independent investigator with unique interdisciplinary skills in sleep/OSA epidemiology research.

## Key facts

- **NIH application ID:** 9981805
- **Project number:** 5K01HL143034-03
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Tianyi Huang
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $177,068
- **Award type:** 5
- **Project period:** 2018-08-20 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9981805

## Citation

> US National Institutes of Health, RePORTER application 9981805, Elucidating Inflammatory and Metabolic Pathways in Obstructive Sleep Apnea Development (5K01HL143034-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9981805. Licensed CC0.

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