Department of Rheumatology and Immunology, Zhuji People's Hospital of Zhejiang Province, 311800, Zhuji, China.
School of Public Health, Hangzhou Medical College, 481 Binwen Road, 310053, Hangzhou, Zhejiang, China.
Genes Genomics. 2022 Jul;44(7):843-853. doi: 10.1007/s13258-022-01239-8. Epub 2022 May 27.
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.
To investigate the causal relationship of PA with serum urate concentrations and gout risk by a bidirectional Mendelian randomization (MR) approach.
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.
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.
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.
身体活动（PA）被认为在降低痛风风险方面发挥着重要作用。然而，流行病学研究结果并不一致，因果关系尚不清楚。
通过双向孟德尔随机化（MR）方法研究 PA 与血清尿酸浓度和痛风风险的因果关系。
使用来自英国生物库的两项全基因组关联研究（GWAS）来识别自我报告的中等到剧烈的 PA（包括 377234 名欧洲个体）、加速度计测量的“平均加速度”PA（包括 91084 名欧洲个体）和加速度计测量的总体 PA（包括 91105 名欧洲个体）的工具变量。血清尿酸（包括 110347 名欧洲个体）和痛风（包括 2115 例病例和 67259 例对照）的汇总数据来自全球尿酸遗传学联合会的 GWAS。此外，还进行了反向孟德尔随机化研究。我们使用的方法包括逆方差加权、加权中位数、孟德尔随机化 Egger 回归、简单模式和加权模式以及孟德尔随机化 pleiotropy RESidual Sum and Outlier。
加速度计测量的“平均加速度”PA（β=-0.038；95%置信区间[CI]：-0.060，-0.015；P=0.001）和加速度计测量的总体 PA（β=-0.339；95%CI：-0.522，-0.156；P=2.8E-4）的遗传易感性与血清尿酸浓度降低显著相关。此外，没有证据支持 PA 与痛风风险之间的因果关系。在反向分析中，尿酸和痛风的遗传易感性与所研究的 PA 没有关联。
在 MR 研究中，我们发现 PA 可能降低血清尿酸浓度，但不能降低痛风风险。此外，血清尿酸浓度和痛风与 PA 无关。
