Genetic Evidence for Causal Association Between Hypertension and Chronic Pain:A Bidirectional Two-Sample Mendelian Randomization Study

高血压与慢性疼痛因果关联的遗传证据:一项双向两样本孟德尔随机化研究

Objective The extent to which the association between hypertension and chronic pain in observational studies is either causally linked or influenced by other shared risk factors has not been substantially addressed.In the present study,Mendelian randomization(MR)was employed to examine the potential causal relationship between hypertension and risk of chronic pain.Methods The study data were derived from the pooled dataset of the genome-wide association study(GWAS),enabling the evaluation of the causal effects of hypertension on various types of chronic pain including chronic headache as well as chest,abdominal,joint,back,limb,and multisite chronic pain.We performed a bidirectional two-sample MR analysis using random effect inverse variance weighting(IVW),MR-Egger,weighted median,and weighted mode,quantified by odds ratio(OR).Results Genetically predicted essential hypertension was associated with an increased risk of chronic headache(OR=1.007,95%CI:1.003-1.011,P=0.002)and limb pain(OR=1.219,95%CI:1.033-1.439,P=0.019).No potential causal associations were identified between chronic pain and essential hypertension in the reverse direction MR(P>0.05).In addition,there was no potential causal association between secondary hypertension and chronic pain(P>0.05).Conclusion This study provided genetic evidence that a unidirectional causal relationship exists between essential hypertension and the increased risks of chronic headache and limb pain,and no causal relationship was found between secondary hypertension and chronic pain.These findings offer theoretical underpinnings for future research on managing hypertension and chronic pain.

目的高血压与慢性疼痛之间是否具有因果关系,或是否受到其他共同风险因素的影响,在观察性研究中尚未得到充分解决。本研究采用孟德尔随机化(Mendelianrandomization,MR)方法来探讨二者间的潜在因果关系。方法研究数据来源于全基因组关联研究(Genome-WideAssociation Study,GWAS)汇总数据集,评估了高血压和多种类型慢性疼痛(包括头痛以及胸部、腹部、关节、背部、四肢和多部位慢性疼痛)之间的因果效应。使用随机效应逆方差加权、MR-Egger、加权中位数和加权众数进行了双向两样本MR分析,并以比值比(odds ratio,OR)进行量化。结果基因预测的原发性高血压与慢性头痛(OR=1.007,95%CI:1.003-1.011,P=0.002)和四肢痛(OR=1.219,95%CI:1.033-1.439,P=0.019)风险增加相关。在反向MR分析中,未发现慢性疼痛与原发性高血压之间存在潜在因果关联(P>0.05)。此外,未发现继发性高血压与慢性疼痛之间存在潜在因果关系(P>0.05)。结论本研究提供了原发性高血压与慢性头痛和四肢痛风险增加之间存在单向因果关系的遗传证据,且未发现继发性高血压与慢性疼痛之间存在因果关系。这些发现为未来在高血压和慢性疼痛管理方面的研究提供了重要的理论依据。