Exploring the causal relationship between antihypertensive drugs and glioblastoma by combining drug target Mendelian randomization study, eQTL colocalization, and single‐cell RNA sequencing

• DOI: 10.1002/tox.24210
• Publication Date: 2024-03-07T11:13:42Z
• Authors: Songyun Zhao; Yi Xie; Xu Ding; Chuanhua Zheng; Jiaxing Chen; Ning Zhao; Yi Ji; Qi Wang; Yuankun Liu; Chao Cheng
• Keywords: Mendelian Randomization; Antihypertensive drug; Genome-wide Association Study

Abstract Recent reports indicate a potential oncogenic role of antihypertensive drugs in common cancers. However, it remains uncertain whether this phenomenon influences the risk glioblastoma multiforme (GBM). This study aimed to assess causal effects blood pressure (BP) and on GBM. Genome‐wide association (GWAS) summary statistics for systolic (SBP), diastolic (DBP), GBM Europeans were downloaded. To represent drugs, we utilized single nucleotide polymorphisms (SNPs) associated with SBP/DBP adjacent coding regions different as instrumental variables model five including angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, calcium channel β‐receptor blockers (BBs), thiazide diuretics. Positive control studies performed using GWAS data chronic heart failure. The primary method causality estimation was inverse‐variance‐weighted method. Mendelian randomization analysis showed that BBs β1‐adrenergic (ADRB1) therapeutic target could significantly reduce by mediating DBP (OR = 0.431, 95% CI: 0.267–0.697, p < .001) they also SBP 0.595, 0.422–0.837, .003). Sensitivity colocalization reinforced robustness these findings. Finally, low expression ADRB1 gene malignant gliomas found from TCGA single‐cell RNA sequencing, which most likely contributed poor prognosis patients. In summary, our provides preliminary evidence some relationship between ADRB1‐targeted development. more are needed validate findings further reveal complex BP