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CLINICAL RESEARCH
Mendelian randomization analysis of the causal relationship between trimethylamine N oxide and its precursors and Parkinson’s disease
1
Center for Cardiovascular and Cerebrovascular Epidemiology and Translational Medicine, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
2
Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo No. 2 Hospital, Ningbo, China
3
Department of Rehabilitation Medicine, Ningbo No. 2 Hospital, Ningbo, China
4
Department of Neurology, Ningbo No. 2 Hospital, Ningbo, China
5
Department of Global Health, Institute of Life and Health Industry, University of Chinese Academy of Sciences, Zhejiang, China
Submission date: 2023-11-03
Final revision date: 2024-01-31
Acceptance date: 2024-02-15
Online publication date: 2024-12-16
Corresponding author
Liyuan Han
Department of Global Health, Institute of Life and Health Industry, University of Chinese Academy of Sciences, Zhejiang, PR China, China
Department of Global Health, Institute of Life and Health Industry, University of Chinese Academy of Sciences, Zhejiang, PR China, China
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Previous studies have reported a potential association between trimethylamine N-oxide (TMAO) and Parkinson’s disease (PD). The objective of this study was to examine the potential relationship between the levels of circulating TMAO and its precursors and the risk of PD using a two-sample Mendelian randomization (MR) approach.
Material and methods:
We aggregated data from three genome-wide association studies (International Parkinson’s Disease Genomics Consortium, Parkinson’s Research: The Organized Genetics Initiative and GenePD, and FinnGen) to extract single-nucleotide polymorphisms (SNPs) associated with circulating concentrations of TMAO, choline, carnitine, and betaine. These SNPs were employed as instrumental variables in a random-effects model to evaluate the causal relationship between circulating concentrations of TMAO and its precursors and the risk of Parkinson’s disease, by estimating odds ratios with accompanying 95% confidence intervals. The primary analysis employed the inverse variance-weighted (IVW) method, which was complemented with MR-Egger regression analysis.
Results:
The analysis using the IVW method, which aggregated data from the three databases, did not show any causal relationship between circulating concentrations of TMAO and its precursors, and the risk of PD (p > 0.05). This finding was further confirmed by the results of the MR-Egger analysis. A sensitivity analysis demonstrated that the results were not influenced by any biases, and a heterogeneity test indicated no significant variation among the SNPs.
Conclusions:
This study did not identify any conclusive evidence of a causal association between the circulating concentrations of TMAO or its precursors and the risk of PD. Further investigation is warranted to determine whether such an association indeed exists.
Previous studies have reported a potential association between trimethylamine N-oxide (TMAO) and Parkinson’s disease (PD). The objective of this study was to examine the potential relationship between the levels of circulating TMAO and its precursors and the risk of PD using a two-sample Mendelian randomization (MR) approach.
Material and methods:
We aggregated data from three genome-wide association studies (International Parkinson’s Disease Genomics Consortium, Parkinson’s Research: The Organized Genetics Initiative and GenePD, and FinnGen) to extract single-nucleotide polymorphisms (SNPs) associated with circulating concentrations of TMAO, choline, carnitine, and betaine. These SNPs were employed as instrumental variables in a random-effects model to evaluate the causal relationship between circulating concentrations of TMAO and its precursors and the risk of Parkinson’s disease, by estimating odds ratios with accompanying 95% confidence intervals. The primary analysis employed the inverse variance-weighted (IVW) method, which was complemented with MR-Egger regression analysis.
Results:
The analysis using the IVW method, which aggregated data from the three databases, did not show any causal relationship between circulating concentrations of TMAO and its precursors, and the risk of PD (p > 0.05). This finding was further confirmed by the results of the MR-Egger analysis. A sensitivity analysis demonstrated that the results were not influenced by any biases, and a heterogeneity test indicated no significant variation among the SNPs.
Conclusions:
This study did not identify any conclusive evidence of a causal association between the circulating concentrations of TMAO or its precursors and the risk of PD. Further investigation is warranted to determine whether such an association indeed exists.
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