Work

Phenome-wide Mendelian Randomization Analysis of Genetic Variants Linking Intracranial Aneurysm, Unruptured Aneurysm, and Subarachnoid Hemorrhage

Year: 2024

Type: preprint

Abstract: Background: Emerging observational studies showed that intracranial aneurysm (IA) was associated with a variety of diseases. However, the causal nature of these associations is uncertain. Method: Based on the GWAS summary data of IA, unruptured IA (UIA) and nontraumatic subarachnoid hemorrhages (SAH), we strictly selected instrumental variables. Through phenotype-wide Mendelian randomization analysis (MR-PheWAS), the association between gene-predicted IA, UIA, SAH and 4057 phenotypes in the UK Biobank study was mapped. The MR-PheWAS association was further examined using data from the FinnGen study (n =260,405). At the same time, we also explored the causal effects of IA, UIA and SAH on the phenotype at the genetic level in reverse. Results: In the MR-PheWAS study of IA, we found that hypertension, difficulty quitting smoking, and use of antihypertensive medications, metabolic characteristics such as diastolic blood pressure, and triglyceride levels significantly increased the risk of IA. Anthropometric characteristics, environmental and neurological factors, and metabolic profiles were significantly associated with UIA risk. Consistent with findings from IA studies, we found that the neurological phenotypes of hypertension and difficulty quitting smoking significantly increased the risk of SAH. These causal associations were still confirmed in the FinnGen study. Conclusion: Our findings help to understand the pathogenesis of these diseases and provide an important basis for developing prevention and treatment strategies. Clinical practice should emphasize management of hypertension, smoking cessation support, and early monitoring and intervention in high-risk patients.

Source: Research Square

DOI: 10.21203/rs.3.rs-5374565/v1

Authors: Aierpati Maimaiti, Lin Pan, Wenzhuo Yang, Laiyu Yang, Leyan Chen, Zibing Zhao, Yongxin Wang, Zengliang Wang

Institutions: First Affiliated Hospital of Xinjiang Medical University, First Hospital of Jilin University, Sun Yat-sen University Cancer Center, Jilin University, Sun Yat-sen University

Language: English

Topic: Intracranial Aneurysms: Treatment and Complications

Subfield: Clinical Neurology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

OpenAlex ID: W4404906992

Cites: 37

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Related to: 10