Mendelian randomization study of causal link from Cerebrospinal fluid metabolomics to neurodegenerative diseases.

Autor: Zhang J; The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China., Zhang X; The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China.; School of Pharmaceutical Sciences, Southern Medical University, 510515, Guangzhou, China., Xiao B; The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China., Ouyang J; The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China., Wang P; The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China. wangpeng20192021@163.com., Peng X; The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, 510900, China. pxb20110607@smu.edu.cn.
Jazyk: angličtina
Zdroj: Neurogenetics [Neurogenetics] 2024 Dec 06; Vol. 26 (1), pp. 15. Date of Electronic Publication: 2024 Dec 06.
DOI: 10.1007/s10048-024-00792-6
Abstrakt: To investigate the causal relationships between cerebrospinal fluid (CSF) metabolites and various neurodegenerative diseases (NDDs), we conducted a two-sample Mendelian randomization (MR) analysis. This study utilized summary statistics from genome-wide association studies (GWAS) of CSF metabolites and four common neurodegenerative diseases: Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). MR methods were employed to determine causal associations, with the inverse variance weighted method as the primary approach. Additionally, different GWAS summary data for NDDs were used to validate the initial results and perform sensitivity analyses to enhance the robustness of the findings. Finally, reverse MR analyses were conducted to assess the possibility of reverse causation. Combining results from the initial and replication phases of MR analysis, we identified potential causal relationships between various CSF metabolites and different NDDs. Specifically, we found potential causal relationships between five CSF metabolites and AD, six CSF metabolites and MS, and thirteen CSF metabolites and ALS. Further sensitivity analyses confirmed the robustness of these associations. Reverse MR analysis indicated causal effects of AD on glucuronate and ALS on acetylcarnitine (C2). Our study, through genetic means, demonstrates close causal associations between the specific types of CSF metabolites and the risk of NDDS (AD, PD, MS, and ALS), providing useful guidance for future clinical researches.
Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Conflict of interest: The authors declare no competing financial interests.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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