Dataset Information

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

ABSTRACT:

Introduction

Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug classes on the risk of IA and SAH.

Materials and methods

Genetic instruments and outcome data were obtained from independent genome-wide association studies (GWAS) or published data, which were exclusively restricted to European ancestry. Causal relationships were identified using inverse-variance weighted MR analyses and a series of statistical sensitivity analyses. The FinnGen consortium was used for repeated analysis to verify results obtained from the above GWAS.

Results

Two-sample MR analysis showed that genetically determined Systolic BP, Dystolic BP, and Pulse Pressure were related to a higher risk of IA and SAH. Based on identified single nucleotide polymorphisms (SNPs) that influence the effect of calcium channel blockers (CCB, 42 SNPs), beta-blockers (BB, 8 SNPs), angiotensin-converting enzyme inhibitors (ACEI, 2 SNPs), angiotensin receptor blockers (ARB, 1 SNPs), and thiazides (5 SNPs), genetically determined effect of CCBs was associated with a higher risk of IA (OR, 1.07 [95% CI, 1.03-1.10], p = 5.02 × 10^-5) and SAH (OR, 1.06 [95% CI, 1.03-1.09], p = 1.84 × 10^-3). No associations were found between other antihypertensive drugs and the risk of IA or SAH. The effect of CCBs on SAH was confirmed in FinnGenconsortium samples (OR, 1.04 [95% CI, 1.00-1.08], p = 0.042).

Discussion and conclusion

This MR analysis supports the role of elevated blood pressure in the occurrence of intracranial aneurysms and subarachnoid hemorrhage. However, genetic proxies for calcium channel blockers were associated with an increased risk of intracranial aneurysms and subarachnoid hemorrhage. Further studies are required to confirm these findings and investigate the underlying mechanisms.

SUBMITTER: Liu H

PROVIDER: S-EPMC10916827 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

Liu Hanchen H Zuo Huiqin H Johanna Ospel O Zhao Rui R Yang Pengfei P Chen Weixing W Li Qiang Q Lin Xiaolei X Zhou Yu Y Liu Jianmin J

European stroke journal 20231006 1

<h4>Introduction</h4>Observational studies suggest that different classes of antihypertensive drugs may have different effects on the occurrence of intracranial aneurysms (IA) and subarachnoid hemorrhage (SAH). However, the reported results in previous studies are inconsistent, and randomized data are absent. We performed a two-sample Mendelian randomization (MR) analysis to study the causal effects of genetically determined blood pressure (BP) and genetic proxies for antihypertensive drug class ...[more]

PMID: 37800876

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Project description:Background and purposeAnimal and observational studies indicate that smoking is a risk factor for aneurysm formation and rupture, leading to nontraumatic subarachnoid hemorrhage (SAH). However, a definitive causal relationship between smoking and the risk of SAH has not been established. Using Mendelian randomization (MR) analyses, we tested the hypothesis that smoking is causally linked to the risk of SAH.MethodsWe conducted a 1-sample MR study using data from the UK Biobank, a large cohort study that enrolled over 500 000 Britons aged 40 to 69 from 2006 to 2010. Participants of European descent were included. SAH cases were ascertained using a combination of self-reported, electronic medical record, and death registry data. As the instrument, we built a polygenic risk score using independent genetic variants known to associate (P<5×10-8) with smoking behavior. This polygenic risk score represents the genetic susceptibility to smoking initiation. The primary MR analysis utilized the ratio method. Secondary MR analyses included the inverse variance weighted and weighted median methods.ResultsA total of 408 609 study participants were evaluated (mean age, 57 [SD 8], female sex, 220 937 [54%]). Among these, 132 566 (32%) ever smoked regularly, and 904 (0.22%) had a SAH. Each additional SD of the smoking polygenic risk score was associated with 21% increased risk of smoking (odds ratio [OR], 1.21 [95% CI, 1.20-1.21]; P<0.001) and a 10% increased risk of SAH (OR, 1.10 [95% CI, 1.03-1.17]; P=0.006). In the primary MR analysis, genetic susceptibility to smoking was associated with a 63% increase in the risk of SAH (OR, 1.63 [95% CI, 1.15-2.31]; P=0.006). Secondary analyses using the inverse variance weighted method (OR, 1.57 [95% CI, 1.13-2.17]; P=0.007) and the weighted median method (OR, 1.74 [95% CI, 1.06-2.86]; P=0.03) yielded similar results. There was no significant pleiotropy (MR-Egger intercept P=0.39; MR Pleiotropy Residual Sum and Outlier global test P=0.69).ConclusionsThese findings provide evidence for a causal link between smoking and the risk of SAH.

Dataset Information

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

Introduction

Materials and methods

Results

Discussion and conclusion

Publications

Genetically determined blood pressure, antihypertensive medications, and risk of intracranial aneurysms and aneurysmal subarachnoid hemorrhage: A Mendelian randomization study.

Similar Datasets

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