Causal associations between neurodegenerative diseases, cardiovascular diseases, cardiovascular risk factors, and lifestyle factors: Evidence from a Mendelian randomization study

Abstract

Introduction: Increasing evidence links cardiovascular disorders (CVDs) and related risk factors to neurodegenerative disease development; however, causal mechanisms are poorly defined.

Objective: This study aims to investigate the causal relationships between neurodegenerative diseases, CVDs, and cardiovascular risk factors, as well as the associations between modifiable lifestyle factors and CVDs and their associated risk factors.

Methods: Single-nucleotide polymorphisms demonstrating associations with neurodegenerative disorders, lifestyle factors, and CVDs were extracted from publicly available genome-wide association study databases.

Results: The findings revealed that Alzheimer’s disease (AD) was negatively associated with pulmonary embolism, heart failure, and type 2 diabetes. In addition, Parkinson’s disease (PD) was linked to an increased risk of hypertension and ischemic stroke. Amyotrophic lateral sclerosis (ALS) correlated positively with hypertension and atrial fibrillation; however, it exhibited a negative relationship with peripheral arterial disease. Coffee intake was positively associated with coronary heart disease, peripheral artery disease, and type 2 diabetes. Alcohol intake was linked to elevated risks of coronary heart disease, hypertension, atrial fibrillation, heart failure, myocardial infarction, and type 2 diabetes. In contrast, tea intake demonstrated inverse associations with coronary heart disease and heart failure.

Conclusion: The present study indicates that ALS, PD, coffee intake, and alcohol intake are associated with an elevated risk of CVDs. Conversely, tea intake demonstrated a protective association against the development of CVDs, whereas AD showed inverse associations with certain cardiovascular risk factors.

Keywords

Alzheimer’s disease / Parkinson’s disease / Amyotrophic lateral sclerosis / Lifestyle factors / Cardiovascular disease / Mendelian randomization

Acknowledgements

The authors express their sincere appreciation to Ms. Becky for her valuable assistance during the preparation of this manuscript.

Funding

This study was supported by the Chifeng Natural Science Foundation (SZR24095) and Wu Jieping Medical Foundation Research Project (320.6750.2024-18-13).

Conflict of interest

The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Author contributions

Conceptualization: Wanying Jia, Jinwei Liu

Formal analysis: Wanying Jia

Funding acquisition: Jinwei Liu

Investigation: Yingnan Zhao

Methodology: Wanying Jia, Tianshu Wu

Software: Wanying Jia, Dongna Wang, Tianming Zhang

Supervision: Haiyan Yu, Hongmei Wang, Jinwei Liu

Visualization: Yingnan Zhao, Guojie Zang

Writing–original draft: Wanying Jia, Tianshu Wu, Yingnan Zhao, Haiyan Yu, Hongmei Wang, Guojie Zang

Writing–review & editing: Dongna Wang, Tianming Zhang, Jinwei Liu

Ethics approval and consent to participate

All genomic data analyzed in this study are sourced from the GWAS public database, which has obtained ethical approval. This database explicitly requires users to assume full responsibility for any materials or content uploaded to the EMBL-EBI data resources and tools.

Consent for publication

This study uses large-scale GWAS summary datasets where all participants gave informed consent in their respective original studies. As we only rely on summary-level statistics, no additional informed consent is required.

Availability of data

Publicly available datasets were analyzed in this study and can be accessed at https://gwas.mrcieu.ac.uk. Supplementary data are available on the Zenodo platform under the DOI: 10.5281/zenodo.16552628.

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