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Genetically predicted physical activity is associated with lower serum urate concentrations

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Abstract

Background

Physical activity (PA) is considered to play an important role in the reduced gout risk. However, the epidemiology results are inconsistent and causality remains unclear.

Objective

To investigate the causal relationship of PA with serum urate concentrations and gout risk by a bidirectional Mendelian randomization (MR) approach.

Method

Two genome-wide association studies (GWASs) from UK Biobank were used to identify instrumental variables for self-reported moderate-to-vigorous PA (including 377,234 European individuals), accelerometer-measured ‘average acceleration’ PA (including 91,084 European individuals) and accelerometer-measured overall PA (including 91,105 European individuals). The summary data for serum urate (including 110,347 European individuals) and gout (including 2,115 cases and 67,259 controls) were derived from GWAS of Global Urate Genetics Consortium. Moreover, reverse direction Mendelian randomization study was conducted. The inverse-variance weighted, weighted median, Mendelian randomization Egger regression, simple mode and weighted mode and Mendelian Randomization Pleiotropy RESidual Sum and Outlier were methods we performed.

Result

Genetic predisposition to accelerometer-measured ‘average acceleration’ PA [beta = -0.038; 95% confidence interval (CI) = -0.060,-0.015; P = 0.001] and accelerometer-measured overall PA (beta = -0.339; 95% CI = -0.522,-0.156; P = 2.8E-4) were significantly associated with decreased serum urate concentrations. Besides, there was no evidence supporting the causal association between PA and gout risk. In the reverse direction analysis, genetic predisposition to both urate and gout were not associated with PA being investigated.

Conclusions

In MR study, we found that PA may reduce serum urate concentrations but not the risk of gout. Moreover, serum urate concentrations and gout were not associated with PA.

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Availability of data and material:

The datasets generated during and/or analyzed during the current studies are available from the corresponding author on reasonable request.

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Acknowledgements

The authors thank all the participants and researchers for their participation in this MR study. All authors interpreted the data, critically revised the manuscript for important intellectual content, approved the final version of the manuscript, and agreed to be responsible for all aspects of the work. The corresponding author attests that all listed co-authors meet authorship criteria and that no others meeting the criteria have been omitted.

Funding

No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this article.

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Authors and Affiliations

  1. Department of Rheumatology and Immunology, Zhuji People’s Hospital of Zhejiang Province, 311800, Zhuji, China

    Ying Guan & Lifeng Meng

  2. School of Public Health, Hangzhou Medical College, 481 Binwen Road, 310053, Hangzhou, Zhejiang, China

    Jiahe Wei, Dingwan Chen & Qilin Qian

  3. Department of Rheumatology and Immunology, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, 310014, Hangzhou, China

    Yasong Li & Tianle Wang

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  1. Ying Guan
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Correspondence to Qilin Qian.

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Guan, Y., Wei, J., Meng, L. et al. Genetically predicted physical activity is associated with lower serum urate concentrations. Genes Genom 44, 843–853 (2022). https://doi.org/10.1007/s13258-022-01239-8

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