Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study

Zhen Zeng; Ting Jin; Jing Ni; Li Huang; Yanqing Xie; Wenming He; Lina Zhang; Changhai Ding; Han Cen

doi:10.1016/j.semarthrit.2022.152095

Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study

Semin Arthritis Rheum. 2022 Dec:57:152095. doi: 10.1016/j.semarthrit.2022.152095. Epub 2022 Sep 9.

Authors

Zhen Zeng¹, Ting Jin¹, Jing Ni², Li Huang³, Yanqing Xie⁴, Wenming He⁵, Lina Zhang⁶, Changhai Ding⁷, Han Cen⁸

Affiliations

¹ Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
² School of Public Health, Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei, Anhui, China.
³ Department of Emergency Intensive Care Unit, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China.
⁴ Department of Cardiology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China.
⁵ Department of Cardiology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China; Institute of Geriatrics, the Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China.
⁶ Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang, China; Institute of Geriatrics, the Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China.
⁷ Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia; Clinical Research Centre, Zhujiang Hospital, Southern Medical University, Guangzhou, China. Electronic address: changhai.ding@utas.edu.au.
⁸ Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang, China; Institute of Geriatrics, the Affiliated Hospital of Medical School, Ningbo University, Ningbo, Zhejiang, China. Electronic address: cenhan@nbu.edu.cn.

PMID: 36126568
DOI: 10.1016/j.semarthrit.2022.152095

Abstract

Objective: Multiple observational studies have reported the close associations of obstructive sleep apnea (OSA) with serum uric acid (SUA) levels and gout. However, the causal nature and direction remains unclear.

Methods: A bidirectional two-sample Mendelian randomization (MR) study was performed, based on publicly available genome-wide association studies (GWAS) summary statistics, to investigate whether OSA is causally related to SUA levels, gout and vice versa. The inverse-variance weighted (IVW) was used as the primary analysis approach, supplemented with four sensitive analysis methods applied to assess the robustness of the results. Moreover, multivariable MR (MVMR) was utilized to evaluate the independent causal effect of OSA on SUA and gout after adjusting for body mass index (BMI), hypertension, type 2 diabetes (T2D), coronary artery disease (CAD), and chronic kidney disease (CKD).

Results: Genetically predicted OSA liability was significantly associated with increased levels of SUA (IVW method: β = 0.19, 95% CI = 0.11 - 0.26, P = 7.24 × 10^-7) and risk of gout [IVW method: odds ratio (OR) = 1.75 95% CI = 1.13 - 2.69, P = 0.01] in univariable MR. The MVMR results suggested that OSA retained its significant association with increased SUA levels, whereas the significant association between OSA and gout was attenuated to null after adjusting for BMI and T2D. No causal effect of OSA on SUA levels and gout was found in the reverse direction.

Conclusions: Our findings suggest that OSA was causally associated with increased levels of SUA, but was not independently associated with gout risk.

Keywords: Causality; Gout; Mendelian randomization; Obstructive sleep apnea; Uric acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / complications
Diabetes Mellitus, Type 2* / genetics
Genome-Wide Association Study
Gout* / genetics
Humans
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Sleep Apnea, Obstructive* / complications
Sleep Apnea, Obstructive* / genetics
Uric Acid

Substances

Uric Acid