Causal relationships between type 1 diabetes mellitus and Alzheimer's disease and Parkinson's disease: a bidirectional two-sample Mendelian randomization study
BackgroundPrevious compelling evidence suggests an association between Type 2 diabetes (T2D) and neurodegenerative diseases. However, it remains uncertain whether Type 1 diabetes mellitus (T1DM) exerts a causal influence on the risk of Alzheimer's disease (AD) and Parkinson's disease (PD). Consequently, this study employed a bidirectional two-sample Mendelian Randomization (MR) approach to investigate the causal relationship between T1DM and the genetic susceptibility to AD and PD.MethodsWe utilized large-scale cohorts derived from publicly available genome-wide association study datasets involving European populations to perform MR analyses. The primary analytical method employed was the inverse-variance weighted (IVW) approach. Furthermore, sensitivity analyses, including assessments of heterogeneity and horizontal pleiotropy, were carried out using Cochran's Q, MR-Egger intercept, and MR-PRESSO tests to enhance the robustness of our conclusions.ResultsUsing the IVW-based method, the MR analysis indicated no significant association between genetically determined T1DM and AD (OR = 0.984, 95% CI: 0.958-1.011, p = 0.247). Conversely, T1DM appeared to be associated with a reduced risk of genetic susceptibility to PD (IVW: OR = 0.958, 95% CI: 0.928-0.989, p = 0.001). In the reverse direction, no evidence of reverse causality was observed between AD (OR = 1.010, 95% CI: 0.911-1.116, p = 0.881) or PD (OR = 1.164, 95% CI: 0.686-2.025, p = 0.5202) and T1DM. Additionally, our analysis found no indications of the results being influenced by horizontal pleiotropy.ConclusionThis MR study reveals that T1DM is associated with a reduced genetic susceptibility to PD, whereas no significant genetic susceptibility is observed between T1DM and AD. These findings suggest that T1DM may have a distinct role in the development of neurodegenerative diseases compared to T2D. Further investigations are warranted to elucidate the underlying mechanisms and provide a more comprehensive understanding of this relationship.
基金:
This work was supported by the National Key Research and Development
Program of China (2022YFC3602600), National Natural Science Foundation of China (82220108009, 81970996), and STI2030-Major Projects
(2021ZD0201801).
第一作者机构:[1]Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, Natl Ctr Neurol Disorders, 45 Changchun St, Beijing 100053, Peoples R China[2]Capital Med Univ, Xuanwu Hosp, Natl Ctr Neurol Disorders, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Capital Med Univ, Xuanwu Hosp, Innovat Ctr Neurol Disorders, Natl Ctr Neurol Disorders, 45 Changchun St, Beijing 100053, Peoples R China[2]Capital Med Univ, Xuanwu Hosp, Natl Ctr Neurol Disorders, Dept Neurol, 45 Changchun St, Beijing 100053, Peoples R China[4]Minist Educ Peoples Republ China, Neurodegenerat Lab, Beijing, Peoples R China
推荐引用方式(GB/T 7714):
Geng Chaofan,Meng Ke,Zhao Bo,et al.Causal relationships between type 1 diabetes mellitus and Alzheimer's disease and Parkinson's disease: a bidirectional two-sample Mendelian randomization study[J].EUROPEAN JOURNAL OF MEDICAL RESEARCH.2024,29(1):doi:10.1186/s40001-023-01628-z.
APA:
Geng, Chaofan,Meng, Ke,Zhao, Bo,Liu, Xiaoduo&Tang, Yi.(2024).Causal relationships between type 1 diabetes mellitus and Alzheimer's disease and Parkinson's disease: a bidirectional two-sample Mendelian randomization study.EUROPEAN JOURNAL OF MEDICAL RESEARCH,29,(1)
MLA:
Geng, Chaofan,et al."Causal relationships between type 1 diabetes mellitus and Alzheimer's disease and Parkinson's disease: a bidirectional two-sample Mendelian randomization study".EUROPEAN JOURNAL OF MEDICAL RESEARCH 29..1(2024)