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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 12; 57:152095.SA

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.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Zeng Z
Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
Jin T
Department of Preventive Medicine, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
Ni J
School of Public Health, Department of Epidemiology and Health Statistics, Anhui Medical University, Hefei, Anhui, China.
Huang L
Department of Emergency Intensive Care Unit, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China.
Xie Y
Department of Cardiology, the Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China.
He W
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.
Zhang L
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.
Ding C
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.
Cen H
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.

MeSH

HumansUric AcidMendelian Randomization AnalysisGenome-Wide Association StudyDiabetes Mellitus, Type 2GoutSleep Apnea, ObstructivePolymorphism, Single Nucleotide

Pub Type(s)

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

Language

eng

PubMed ID

36126568

Citation

Zeng, Zhen, et al. "Assessing the Causal Associations of Obstructive Sleep Apnea With Serum Uric Acid Levels and Gout: a Bidirectional Two-sample Mendelian Randomization Study." Seminars in Arthritis and Rheumatism, vol. 57, 2022, p. 152095.
Zeng Z, Jin T, Ni J, et al. 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;57:152095.
Zeng, Z., Jin, T., Ni, J., Huang, L., Xie, Y., He, W., Zhang, L., Ding, C., & Cen, H. (2022). Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study. Seminars in Arthritis and Rheumatism, 57, 152095. https://doi.org/10.1016/j.semarthrit.2022.152095
Zeng Z, et al. 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;57:152095. PubMed PMID: 36126568.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessing the causal associations of obstructive sleep apnea with serum uric acid levels and gout: a bidirectional two-sample Mendelian randomization study. AU - Zeng,Zhen, AU - Jin,Ting, AU - Ni,Jing, AU - Huang,Li, AU - Xie,Yanqing, AU - He,Wenming, AU - Zhang,Lina, AU - Ding,Changhai, AU - Cen,Han, Y1 - 2022/09/09/ PY - 2022/07/09/received PY - 2022/08/25/revised PY - 2022/09/05/accepted PY - 2022/9/21/pubmed PY - 2022/11/23/medline PY - 2022/9/20/entrez KW - Causality KW - Gout KW - Mendelian randomization KW - Obstructive sleep apnea KW - Uric acid SP - 152095 EP - 152095 JF - Seminars in arthritis and rheumatism JO - Semin Arthritis Rheum VL - 57 N2 - 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. SN - 1532-866X UR - https://www.unboundmedicine.com/medline/citation/36126568/Assessing_the_causal_associations_of_obstructive_sleep_apnea_with_serum_uric_acid_levels_and_gout:_a_bidirectional_two_sample_Mendelian_randomization_study_ DB - PRIME DP - Unbound Medicine ER -