Related Experiment Video
Updated: Jun 7, 2025
Author Spotlight: Obtaining High-Quality CSF and Blood Samples for Epilepsy Biomarker Discovery
Published on: September 1, 2023
Dissecting the association between blood pressure traits, hypertension, antihypertensive medications and epilepsy: A
Cheng Yu1, Shijiu Jiang2, Bingjie Lv2
1Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
Hypertension causally increases epilepsy risk. Managing diastolic blood pressure (DBP) with beta-blockers may help prevent epilepsy, according to Mendelian randomization studies.
Area of Science:
- Genetics
- Epidemiology
- Pharmacology
Background:
- Observational studies indicate a high co-occurrence of hypertension and epilepsy.
- Antihypertensive medications may influence epilepsy prevention and treatment.
- The causal relationship between hypertension and epilepsy remains unclear.
Purpose of the Study:
- To investigate the causal relationship between hypertension and epilepsy using Mendelian randomization.
- To explore the potential impact of antihypertensive medications on epilepsy risk.
Main Methods:
- Bidirectional univariate and multivariate Mendelian randomization (MR) analyses were performed using genome-wide association studies (GWAS) summary data.
- Sensitivity analyses included Cochran's Q, leave-one-out, MR-Egger, and MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods.
- Drug target MR assessed associations between antihypertensive medication targets and epilepsy risk, utilizing single nucleotide polymorphisms (SNPs) and expression quantitative trait loci (eQTL).
Main Results:
- Genetically predicted blood pressure traits and hypertension demonstrated causal effects on epilepsy.
- Epilepsy did not show causal impacts on blood pressure traits or hypertension.
- Beta-blocker target genes, particularly ADRA1D, showed a positive association with epilepsy risk, especially when linked to diastolic blood pressure (DBP).
Conclusions:
- Hypertension is confirmed to have a causal effect on epilepsy.
- Managing diastolic blood pressure in hypertensive patients with beta-blockers may offer a strategy for epilepsy prevention.
Background:
Observational studies suggest that hypertension and epilepsy have a high co-occurrence, and antihypertensive medications may have impacts on the prevention and treatment of epilepsy. However, the directionality of causation between them is elusive.
Method:
By leveraging genome-wide association studies (GWAS) summary data of each trait, we firstly performed bidirectional univariate Mendelian randomization (UVMR) to assess the strength and direction of the associations between pairs of traits, then multivariate MR (MVMR) was conducted to adjust for potential confounders in causalities. Cochran's Q statistics, leave-one-out analysis, MR-Egger regression and MR-Pleiotropy Residual Sum and Outlier methods (MR-PRESSO) were employed to evaluate the robustness of the results. Drug target MR was proceeded to assess the association between five classes of first-line antihypertensive medications and epilepsy. Specifically, single nucleotide polymorphisms (SNPs) extracted from GWAS data on systolic blood pressure (SBP)/diastolic blood pressure (DBP), along with expression quantitative trait loci (eQTL) were utilized as proxies for antihypertensive medications, respectively.
Results:
Forward UVMR results provided evidence that genetically predicted blood pressure traits and hypertension have causal effects on epilepsy, while reverse UVMR indicated no causal impacts of epilepsy on blood pressure traits or hypertension. The sensitivity analysis results were robust. The causalities between DBP, hypertension and epilepsy remained remarkable after adjustment by MVMR. Inverse-variance-weighted MR (IVW-MR) yielded evidence of positive association only between Beta-Blockers target genes based on DBP GWAS screening and epilepsy. Summary-data-based MR (SMR) identified a positive correlation between Beta-Blockers target gene ADRA1D and epilepsy risk.
Conclusions:
Hypertension has a causal effect on epilepsy and managing DBP in patients with hypertension through Beta-Blockers may help prevent epilepsy.
Related Concept Videos
01:24Arteries of the Lower Limbs
Various factors can trigger epilepsy, including genetic factors, brain damage, metabolic causes, and unknown etiology. Diagnosis of epilepsy involves electroencephalography (EEG), which...
01:18Hypertension and Regulation of Blood Pressure
01:28Factors affecting Blood pressure
Physiological Factors:
01:28Antihypertensive Drugs: Potassium-Sparing Diuretics
01:17Antiepileptic Drugs: Calcium Channel Blockers
Calcium channel blockers exert their antiepileptic effects by targeting T-type calcium channels, which are integral to transmitting nerve signals in the central nervous system. These channels allow the passage of calcium ions, which are vital for neuronal communication. By inhibiting T-type calcium channels, calcium channel blockers effectively reduce the release of neurotransmitters and...
01:09Epistasis Analysis