Drug classes affecting intracranial aneurysm risk: Genetic correlation and Mendelian randomization.

IF 5.8 3区医学 Q1 CLINICAL NEUROLOGY

European Stroke Journal Pub Date : 2024-09-01 Epub Date: 2024-02-15 DOI:10.1177/23969873241234134

Ynte M Ruigrok, Jan H Veldink, Mark K Bakker

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引用次数: 0

Abstract

Introduction: There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach.

Patients and methods: Using genome-wide association summary statistics we calculated genetic correlation between unruptured IA (N = 2140 cases), ASAH (N = 5140) or the combined group, and liability to drug usage from 23 drug classes (N up to 320,000) independent of the risk factor high blood pressure. Next, we evaluated the causality and therapeutic potential of correlated drug classes using three different Mendelian randomization frameworks.

Results: Correlations with IA were found for antidepressants, paracetamol, acetylsalicylic acid, opioids, beta-blockers, and peptic ulcer and gastro-esophageal reflux disease drugs. MR showed no evidence that genetically predicted usage of these drug classes caused IA. Genetically predicted high responders to antidepressant drugs were at higher risk of IA (odds ratio [OR] = 1.61, 95% confidence interval (CI) = 1.09-2.39, p = 0.018) and ASAH (OR = 1.68, 95% CI = 1.07-2.65, p = 0.024) if they used antidepressant drugs. This effect was absent in non-users. For beta-blockers, additional analyses showed that this effect was not independent of blood pressure after all. A complex and likely pleiotropic relationship was found between genetic liability to chronic multisite pain, pain medication usage (paracetamol, acetylsalicylic acid, and opioids), and IA.

Conclusions: We did not find drugs decreasing liability to IA and ASAH but found that antidepressant drugs may increase liability. We observed pleiotropic relationships between IA and other drug classes and indications. Our results improve understanding of pathogenic mechanisms underlying IA.

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影响颅内动脉瘤风险的药物类别：遗传相关性和孟德尔随机化。

导言：目前还没有一种非侵入性治疗方法可以预防由颅内动脉瘤（IA）破裂引起的动脉瘤性蛛网膜下腔出血（ASAH）。我们的目的是利用遗传学方法确定可能影响颅内动脉瘤易感性的药物类别：利用全基因组关联汇总统计，我们计算了未破裂IA（2140例）、ASAH（5140例）或合并组与23类药物（多达32万种）的药物使用责任之间的遗传相关性，而与高血压这一风险因素无关。接下来，我们使用三种不同的孟德尔随机框架评估了相关药物类别的因果关系和治疗潜力：结果：发现抗抑郁药、扑热息痛、乙酰水杨酸、阿片类药物、β-受体阻滞剂、消化性溃疡和胃食管反流病药物与内分泌相关。磁共振结果显示，没有证据表明基因预测的这些药物类别的使用会导致内分泌失调。基因预测的抗抑郁药物高反应者如果使用抗抑郁药物，罹患IA（几率比[OR] = 1.61，95% 置信区间（CI）= 1.09-2.39，p = 0.018）和ASAH（OR = 1.68，95% CI = 1.07-2.65，p = 0.024）的风险较高。未使用抗抑郁药物者则无此效应。对于β-受体阻滞剂，额外的分析表明这种效应与血压无关。我们发现，慢性多部位疼痛的遗传易感性、止痛药（扑热息痛、乙酰水杨酸和阿片类药物）的使用与内分泌之间存在复杂且可能是多效应的关系：结论：我们没有发现药物会降低对 IA 和 ASAH 的易感性，但发现抗抑郁药物可能会增加易感性。我们观察到原发性血管炎与其他药物类别和适应症之间的多效应关系。我们的研究结果增进了人们对诱发原发性心绞痛的致病机制的了解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

European Stroke Journal Multiple-

CiteScore

7.50

自引率

6.60%

发文量

102

期刊介绍： Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.