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评估脉压对偏头痛风险的因果效应:一项孟德尔随机化研究。

Assessing the Causal Effect of Pulse Pressure on Migraine Risk: A Mendelian Randomization Study.

作者信息

Xu Hongli, Qin Xiaoyan, Feng Zeguo, You Shaohua

机构信息

Medical Big Data Research Center, Medical Innovation Research Department of PLA General Hospital, Beijing, 100853, People's Republic of China.

Department of Clinical Laboratory, Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, 100049, People's Republic of China.

出版信息

J Pain Res. 2025 Jun 25;18:3159-3170. doi: 10.2147/JPR.S512795. eCollection 2025.

DOI:10.2147/JPR.S512795
PMID:40584772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12206417/
Abstract

BACKGROUND

Migraine is notably prevalent among young individuals and women, who generally demonstrate favorable arterial compliance. Pulse pressure is a reliable measure of arterial compliance; nevertheless, the association between pulse pressure and migraine is not well understood.

AIM

To investigate the potential causal relationship between pulse pressure and the risk of migraine using Mendelian randomization (MR).

METHODS

The pulse pressure studies mainly involved participants of European descent, while the migraine studies included individuals from various parts of the UK. The primary analysis used Inverse Variance Weighted (IVW) method, supplemented by weighted median and MR-Egger regression. Validation data came from the FinnGen study. Genes linked to pulse pressure were analyzed for Gene Ontology (GO) and KEGG enrichment using the DAVID platform.

RESULTS

Single-nucleotide polymorphisms linked to pulse pressure were sourced from a GWAS database (810,865 individuals), while migraine data came from UK Biobank (13,971 cases, 470,627 controls). The IVW method showed an OR of 0.992 [95% confidence interval (CI), 0.987-0.997; 0.002]. Both weighted median (OR 0.988; 95% CI, 0.982-0.994; < 0.001) and MR-Egger (OR 0.985; 95% CI, 0.972-0.997; 0.016) analyses confirmed a negative causal link between pulse pressure and migraine risk. The MR-Egger intercept analysis showed minimal evidence of horizontal pleiotropy (b = 0.00013, SE = 0.00010, 0.209). Finnish data confirmed a causal link between migraine and pulse pressure, with the IVW method indicating a significant association (OR = 0.790, 95% CI: 0.676-0.922; = 0.003). KEGG enrichment analysis revealed significant pathways regulating pulse pressure, many related to cardiovascular disease and type 2 diabetes.

CONCLUSION

MR analysis showed that pulse pressure causally affects migraines, potentially explaining why young people and women experience more migraines, while those with type 2 diabetes have a lower risk. Further research is needed to understand this relationship.

摘要

背景

偏头痛在年轻人和女性中尤为普遍,他们通常表现出良好的动脉顺应性。脉压是动脉顺应性的可靠指标;然而,脉压与偏头痛之间的关联尚未得到充分理解。

目的

使用孟德尔随机化(MR)研究脉压与偏头痛风险之间的潜在因果关系。

方法

脉压研究的主要参与者为欧洲血统,而偏头痛研究的对象包括来自英国各地的个体。主要分析采用逆方差加权(IVW)方法,并辅以加权中位数和MR-Egger回归。验证数据来自芬兰基因研究。使用DAVID平台对与脉压相关的基因进行基因本体论(GO)和KEGG富集分析。

结果

与脉压相关的单核苷酸多态性来自一个全基因组关联研究(GWAS)数据库(810,865人),而偏头痛数据来自英国生物银行(13,971例病例,470,627例对照)。IVW方法显示比值比为0.992[95%置信区间(CI),0.987 - 0.997;P = 0.002]。加权中位数分析(比值比0.988;95% CI,0.982 - 0.994;P < 0.001)和MR-Egger分析(比值比0.985;95% CI,0.972 - 0.997;P = 0.016)均证实脉压与偏头痛风险之间存在负因果关系。MR-Egger截距分析显示水平多效性的证据极少(b = 0.00013,标准误 = 0.00010,P = 0.209)。芬兰的数据证实了偏头痛与脉压之间的因果关系,IVW方法显示存在显著关联(比值比 = 0.790,95% CI:0.676 - 0.922;P = 0.003)。KEGG富集分析揭示了调节脉压的重要途径,许多与心血管疾病和2型糖尿病相关。

结论

MR分析表明脉压对偏头痛有因果影响,这可能解释了为什么年轻人和女性更容易患偏头痛,而2型糖尿病患者的风险较低。需要进一步研究以了解这种关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/eb612f201079/JPR-18-3159-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/b40291007009/JPR-18-3159-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/0d63b4b4cf71/JPR-18-3159-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/bcc4c05338c0/JPR-18-3159-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/722a768b0b0a/JPR-18-3159-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/eb612f201079/JPR-18-3159-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/b40291007009/JPR-18-3159-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/0d63b4b4cf71/JPR-18-3159-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/bcc4c05338c0/JPR-18-3159-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/722a768b0b0a/JPR-18-3159-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d813/12206417/eb612f201079/JPR-18-3159-g0005.jpg

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本文引用的文献

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Causality between migraine and cardiovascular disease: a bidirectional Mendelian randomization study.偏头痛与心血管疾病之间的因果关系:一项双向孟德尔随机化研究。
J Headache Pain. 2024 Aug 13;25(1):130. doi: 10.1186/s10194-024-01836-w.
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European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol.欧洲头痛联合会(EHF)对偏头痛预防中的口服药物的关键性再评估和荟萃分析 - 第 4 部分:普萘洛尔。
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Cohort profile: migraine exposures and cardiovascular health in Hong Kong Chinese women (MECH-HK).
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A phenome-wide association and Mendelian randomisation study of alcohol use variants in a diverse cohort comprising over 3 million individuals.在一个由超过 300 万人组成的多样化队列中,对饮酒相关变体进行全基因组关联和孟德尔随机化研究。
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