Dataset Information

Association between Type 1 Diabetes Mellitus and Parkinson's Disease: A Mendelian Randomization Study.

ABSTRACT: While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson's disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a lower risk of PD in T1DM (IVW-OR 0.93, 95% CI 0.91-0.96, p = 3.12 × 10^-5; MR-Egger-OR 0.93, 95% CI 0.88-0.98, p = 1.45 × 10^-2; weighted median-OR 0.93, 95% CI 0.89-0.98, p = 2.76 × 10^-3; and weighted mode-OR 0.94, 95% CI 0.9-0.98, p = 1.58 × 10^-2). The findings were then replicated with another independent GWAS dataset on T1DM (IVW-OR 0.97, 95% CI 0.95-0.99, p = 3.10 × 10^-3; MR-Egger-OR 0.96, 95% CI 0.93-0.99, p = 1.08 × 10^-2; weighted median-OR 0.97, 95% CI 0.94-0.99, p = 1.88 × 10^-2; weighted mode-OR 0.97, 95% CI 0.94-0.99, p = 1.43 × 10^-2). Thus, our study provides evidence that T1DM may have a protective effect on PD risk, though further studies are needed to clarify the underlying mechanisms.

SUBMITTER: Mai AS

PROVIDER: S-EPMC10816052 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between Type 1 Diabetes Mellitus and Parkinson's Disease: A Mendelian Randomization Study.

Mai Aaron Shengting AS Tan Brendan Jen-Wei BJ Sun Qiao-Yang QY Tan Eng-King EK

Journal of clinical medicine 20240118 2

While much evidence suggests that type 2 diabetes mellitus increases the risk of Parkinson's disease (PD), the relationship between type 1 diabetes mellitus (T1DM) and PD is unclear. To study their association, we performed a two-sample Mendelian randomization (MR) using the following statistical methods: inverse variance weighting (IVW), MR-Egger, weight median, and weighted mode. Independent datasets with no sample overlap were retrieved from the IEU GWAS platform. All the MR methods found a l ...[more]

PMID: 38256693

Similar Datasets

Project description: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.

Project description:BackgroundThe presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies.MethodsSummary statistics of T1DM and seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry and FinnGen biobank were extracted for the primary MR analysis, and the analysis was replicated using UK biobank (UKBB) for validation. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs.ResultsCausal effects of T1DM on peripheral atherosclerosis (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02-1.10; p = 0.002)] and coronary atherosclerosis (OR = 1.03, 95% CI: 1.01-1.05; p = 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23-19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35-28.33%). We didn't find significant causal relationships between T1DM and other CVDs, including heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), myocardial infarction (MI) and stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified.ConclusionThis MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.

Project description:BackgroundGestational diabetes mellitus (GDM) constitutes a significant contributor to maternal and fetal morbidity, which is observed to be associated with future risks of offspring health. Nevertheless, it is essential to acknowledge that observational findings may be susceptible to residual confounding and bias.MethodsTo investigate the association of GDM with offspring health, a genome-wide genetic association study employing Mendelian Randomization (MR) is conducted between May 31 and November 30, 2023. The inverse-variance-weighted (IVW) is utilized in the primary analysis stage. The study data of the majority patients are European ancestry, which are sourced from the IEU open genome-wide association study project.ResultsGenetically predicted GDM is associated with an increased risk of various short- and long-term health problem in offspring. For fetal and neonatal conditions, GDM is linked to an elevated risk of preterm delivery [ odd ratio (OR) = 1.150, false discovery rate (FDR)-adjusted PIVW = 0.009] and placental disorders (OR = 2.143, FDR-adjusted PIVW = 0.028). In respiratory diseases, it is associated with a higher likelihood of influenza (OR = 1.175, FDR-adjusted PIVW = 0.008), bacterial pneumonia (OR = 1.141, FDR-adjusted PIVW = 0.008), congenital malformations of the respiratory system (OR = 1.673, FDR-adjusted PIVW = 0.033), influenza with pneumonia (OR = 1.078, FDR-adjusted PIVW = 0.008), and need for non-invasive ventilation (OR = 1.265, FDR-adjusted PIVW = 0.028). In terms of neurodevelopmental and psychiatric outcomes, GDM is linked to a higher risk of cerebral palsy (OR = 1.721, FDR-adjusted PIVW = 0.008). For urinary conditions, GDM increases the risk of acute tubulo-interstitial nephritis (OR = 1.098, FDR-adjusted PIVW = 0.008). No association is identified between genetically predicted GDM and major digestive diseases, such as gastroesophageal reflux, or cardiovascular conditions in offspring.ConclusionsThe findings of this study provide genetic evidence supporting an association between GDM and higher risk of offspring diseases. This supports classification of GDM as risk factors for short- and long-term offspring health.

Dataset Information

Association between Type 1 Diabetes Mellitus and Parkinson's Disease: A Mendelian Randomization Study.

Publications

Association between Type 1 Diabetes Mellitus and Parkinson's Disease: A Mendelian Randomization Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets