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. 2023 Sep 29:15:749-765.
doi: 10.2147/NSS.S423331. eCollection 2023.

How is Obstructive Sleep Apnea Associated with High Blood Pressure and Diabetes Mellitus Type 2? Clues from a Two-Step Mendelian Randomized Study

Yubin Shen #  1 , Hongwei Wang #  1 , Weiyu Zhang  1 , Xiwen Ou  1 , Song Liu  1
Affiliations

How is Obstructive Sleep Apnea Associated with High Blood Pressure and Diabetes Mellitus Type 2? Clues from a Two-Step Mendelian Randomized Study

Yubin Shen et al. Nat Sci Sleep. .

Abstract

Background: Obstructive sleep apnea (OSA), high blood pressure (HBP), and type 2 diabetes mellitus (T2DM) have a close clinical relationship, but whether and how OSA affects HBP and T2DM is unclear.

Study design and methods: Two-step, two-sample Mendelian randomization techniques were applied using single-nucleotide polymorphisms as genetic instruments for exposure and mediators, thus minimizing bias due to confounding factors and reverse causality. The total effect of OSA on HBP and T2DM was categorized into direct and mediating effects based on the mediating factors.

Results: Two-sample MR analysis showed that OSA increased the risk of HBP (odds ratio [OR] = 1.010, 95% confidence interval [CI], 1.002-1.018; P = 0.0121) and T2DM (OR = 1.140, 95% CI, 1.059-1.228; P = 0.0005). In the process of OSA caused by HBP, sex hormone-binding globulin (SHBG) (female, 4.47% mediation; male, 2.76% mediation), total testosterone (TT) (male, 3.72% mediation), bioavailable testosterone (BioT) (female, 7.74% mediation), high-density lipoprotein cholesterol (HDL-C) (3.25% mediation), and apolipoprotein A1 (ApoA1) (1.31% mediation) were individual contributors. SHBG (female, 4.10% mediation; male, 1.58% mediation), TT (male, 3.69% mediation), BioT (female, 2.58% mediation), HDL-C (3.32% mediation), ApoA1 (2.14% mediation), and omega-6 fatty acids (2.33% mediation) may have mediating roles to varying degrees in the process of OSA caused by T2DM.

Interpretation: This MR study showed that OSA is a risk factor for HBP and T2DM, and the evaluation of mediators may help further reveal the specific mechanism by which OSA causes HBP and T2DM.

Keywords: Mendelian randomization; high blood pressure; mediating factors; obstructive sleep apnea; type 2 diabetes mellitus.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Directed acyclic graph of the MR framework investigating the causal relationship between OSA and HBP/T2DM. Instrumental variable assumptions: (1) the GIVs must be strongly associated with OSA; (2) the GIVs must not be associated with any potential confounder of OSA versus HBP/T2DM relationship; (3) the GIVs should only affect the risk of HBP/T2DM through OSA.
Figure 2
Figure 2
(A) Associations of genetic liability to OSA with the risk of HBP. Forest plot to visualize causal effects of variation in OSA on HBP. β/OR and CI correspond to the effects of OSA on HBP. The results of MR analyses using IVW-RE (B) and cML-MA-BIC (C) analysis methods are compared. Total SNP indicates the number of genetic variants used as instruments for MR analysis.
Figure 3
Figure 3
(A) Associations of genetic liability to OSA with the risk of T2DM. Forest plot to visualize causal effects of variation in OSA on T2DM. β/OR and CI correspond to the effects of OSA on T2DM. The results of MR analyses using IVW-RE (B) and cML-MA-BIC (C) analysis methods are compared. Total SNP indicates the number of genetic variants used as instruments for MR analysis.
See this image and copyright information in PMC

References

    1. Kapur VK, Auckley DH, Chowdhuri S, et al. Clinical practice guideline for diagnostic testing for adult obstructive sleep apnea: an American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(3):479–504. doi:10.5664/jcsm.6506 - DOI - PMC - PubMed
    1. Zhang XB, Jiang XT, Du YP, Yuan YT, Chen B, Atkin SL. Efficacy of continuous positive airway pressure on testosterone in men with obstructive sleep apnea: a meta-analysis. PLoS One. 2014;9(12):e115033. doi:10.1371/journal.pone.0115033 - DOI - PMC - PubMed
    1. Alvarenga TA, Fernandes GL, Bittencourt LR, Tufik S, Andersen ML. The effects of sleep deprivation and obstructive sleep apnea syndrome on male reproductive function: a multi-arm randomised trial. J Sleep Res. 2022;32(1):e13664. doi:10.1111/jsr.13664 - DOI - PubMed
    1. Zhang Y, Elgart M, Kurniansyah N, et al. Genetic determinants of cardiometabolic and pulmonary phenotypes and obstructive sleep apnoea in HCHS/SOL. EBioMedicine. 2022;84:104288. doi:10.1016/j.ebiom.2022.104288 - DOI - PMC - PubMed
    1. Zhang J, Chen Z, Parna K, van Zon SKR, Snieder H, Thio CHL. Mediators of the association between educational attainment and type 2 diabetes mellitus: a two-step multivariable Mendelian randomisation study. Diabetologia. 2022;65(8):1364–1374. doi:10.1007/s00125-022-05705-6 - DOI - PMC - PubMed