Research Paper Volume 15, Issue 23 pp 14039—14065

Association of modifiable risk factors with obstructive sleep apnea: a Mendelian randomization study

Ye Li1,2, *, , Yuyang Miao1,2, *, , Jin Tan1,2, , Qiang Zhang1,2, ,

  • 1 Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 300052, China
  • 2 Tianjin Geriatrics Institute, Tianjin 300052, China
* Equal contribution

Received: July 6, 2023       Accepted: October 16, 2023       Published: December 11, 2023      

https://doi.org/10.18632/aging.205288
How to Cite

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: The risk factors involved in obstructive sleep apnea (OSA) have not been clearly identified yet. We attempted to systematically investigate genetically predicted modifiable risk factors and lifestyle behaviors associated with OSA.

Methods: The association between 34 risk factors and OSA was evaluated using the two-sample Mendelian randomization (MR). Genetic variants for risk factors were acquired from European-descent genome-wide studies. Data sources for OSA were extracted from FinnGen study with 16,761 cases and 201,194 controls. The primary analysis chosen was the inverse-variance weighted method.

Results: MR analyses provide evidence of genetically predicted poor overall health rating (odds ratio (OR), 2.82; 95% confidence interval (CI), 1.95–4.08), nap during day (OR, 2.01; 95% CI, 1.37–2.93), high body mass index (BMI) (OR, 1.14; 95% CI, 1.09–1.19), increased body fat mass (OR, 1.83; 95% CI, 1.83–2.05), elevated body water mass (OR, 1.50; 95% CI, 1.31–1.70) and hypertension (OR, 1.81; 95% CI, 1.34–2.45) were associated with higher OSA risk, while high education level (OR, 0.55; 95% CI, 0.40–0.75) correlated with reduced OSA risk. Suggestive evidence was obtained for smoking and waist-to-hip ratio (WHR) with higher OSA odds, and vigorous physical activity, and HDL cholesterol with lower OSA odds. After adjusting for BMI using multivariable MR analysis, the effects of smoking, WHR, vigorous physical activity, and HDL-cholesterol were fully attenuated.

Conclusions: This MR study indicates that overall health rating, nap during day, BMI, body fat mass, body water mass, hypertension, and education are causally associated with the risk of OSA, which means that these modifiable risk factors are key targets for OSA prevention.

Abbreviations

MR: Mendelian randomization; SNPs: single nucleotide polymorphisms; IVs: instrumental variables; GWAS: genome-wide association studies; IVW: the inverse variance weighted; MR-PRESSO: Mendelian Randomization Pleiotropy RESidual Sum and Outlier; OR: odds ratio; Cis: confidence intervals; OSA: obstructive sleep apnea; WHR: waist-to-hip ratio; BMI: body mass index; HDL-c: high-density lipoprotein cholesterol; AHI: apnea-hypopnea index; REI: respiratory event index.