基于两样本孟德尔随机化方法探讨睡眠与痛风的关联

The Association of Sleep Related Phenotypes with the Risk of Gout:Two-sample Mendelian Randomization

[目的]通过两样本孟德尔随机化设计,探讨睡眠与痛风之间的关联。[方法]从一项包含763813名参与者的全基因组关联研究(genome-wide association study,GWAS)中获取痛风遗传关联数据。以与打鼾、睡眠时间、睡眠类型、失眠及白日困倦程度等睡眠表型相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量,采用逆方差加权(inverse variance weighted,IVW)评估遗传学预测的不同睡眠表型与痛风发生风险的关系。采用MR-Egger回归和孟德尔随机多态性残差和离群值(MR pleiotropy residual sum and outlier,MR-PRESSO)检验进行敏感性分析,以评估工具变量的多效性。进一步采用加权中位数法、简单中位数法、最大似然比法等分析方法检验结果的稳健性与可靠性。[结果]IVW结果显示,遗传学预测的打鼾[优势比(odds ratio,OR)=3.12,95%置信区间(confidence interval,CI)(1.21~8.05),PFDR=0.045]和失眠[OR=1.09,95%CI(1.04~1.15),PFDR=0.005]与痛风发生风险呈正相关,而睡眠时间、睡眠类型及白日困倦程度与痛风发生之间不存在统计学关联。MR-Egger回归提示上述因果关联未受到水平多效性影响,加权中位数法、简单中位数法、最大似然比法得出与IVW相似的结果。[结论]打鼾、失眠与痛风发生风险呈正相关,纠正打鼾和失眠可能对痛风有一定的预防作用。

[Objective]To explore the potential causal associations between sleep-related phenotypes and the risk of gout by using two-sample Mendelian randomization.[Methods]The summary statistics for gout were obtained from a genome-wide association study(GWAS)of 763813 participants.The single nucleotide polymorphisms(SNP)associated with five sleep phenotypes,namely snoring,sleep duration,chronotype,insomnia and daytime sleepiness,were used as instrumental variables(IV).The inverse variance weighted(IVW)method was used to assess the associations between sleep phenotypes and the risk of gout.The MR-Egger regression and MR pleiotropy residual sum and outlier(MR-PRESSO)test were used to estimate the pleiotropy of SNPs.The weighted median,simple-median and likelihood-based methods were applied to further test the robustness and reliability of the results.[Results]The IVW approach showed that the genetically predicted snoring[odds ratio(OR)=3.12,95%confidence interval(CI)(1.21~8.05),PFDR=0.045)],insomnia[(OR=1.09,95%CI(1.04~1.15),PFDR=0.005)]were positively associated with the risk of gout.However,no statistically significant associations of sleep duration,chronotype and daytime sleepiness with the risk of gout were observed.MR-Egger regression did not indicate the horizontal pleiotropy in the above associations,and the weighted median,simple-median and likelihood-based methods yielded similar results to the IVW method.[Conclusion]The current study suggested that snoring and insomnia were positively associated with the risk of gout,suggesting that the treatment on snoring and insomnia may reduce the incidence of gout.