Causal role of immune cells on risk of Parkinson’s disease: a Mendelian randomization study

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: March 22, 2024

Previous observational studies have suggested a correlation between immune cells and Parkinson's disease (PD), yet specific investigations into the causal relationship two remain limited. This study aims to explore this potential relationship. We utilized genome-wide association (GWAS) data on Disease, conducting two-sample Mendelian randomization (MR) analysis using single nucleotide polymorphisms (SNPs). To estimate causality, we employed inverse variance weighting (IVW), MR-Egger, weighted median (WM) methods. For sensitivity analysis, used Cochran's Q-test, MR-Egger intercept, leave-one-out funnel plots. After false discovery rate (FDR) correction, effects of PD cells, vice versa, were not statistically significant. These include CX3CR1 CD14+ CD16-monocyte (OR = 0.91, 95% CI 0.86-0.96, p 0.0003 PFDR 0.152), CD62L-CD86+ myeloid DC AC 0.93, 0.89-0.97, 0.0005, 0.152),CD11b Mo 1.08, 1.03-1.13, 0.001, CD38 igd+ cd24- 1.14, 1.06-1.23, D14+ cd16+ monocyte %monocyte 1.10, 1.04-1.17, 0.159). Additionally, may be causally related phenotype CM CD8br %T cell (beta 0.10, 1.14-1.16, 0.0004, 0.151), SSC-A 0.11, 1.15-1.18, 0.1 monocyte). No pleiotropy was determined. link Disease through MR method, which could provide new direction for mechanistic research clinical treatment PD.

Language: Английский

---

Exploring risk factors for autoimmune diseases complicated by non-hodgkin lymphoma through regulatory T cell immune-related traits: a Mendelian randomization study

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 28, 2024

Background The effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) traits and ADs NHL remains debated. Methods Aggregate data for 84 Treg-related were downloaded from the Genome-Wide Association Study (GWAS) catalog, GWAS diffuse large B-cell (DLBCL; n=315243), follicular (FL; n=325831), sjögren’s syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn’s disease(CD; n=411973) systemic lupus erythematosus (SLE; n=307587) FinnGen database. inverse variance weighting (IVW) method was mainly used to infer any association DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD SLE, supplemented MR-Egger, weighted median, simple mode, mode. Moreover, we performed sensitivity analyses assess validity relationships. Results There potential genetic predisposition identified CD39+ CD8br AC, % cell, risk DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed associations CD25++ CD28- CD8br, FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) FDR>0.1). Furthermore, SLE exhibited genetically predicted with CD8+ Tregs subset. SS DM possibly associated an increase in quantity CD4+ subset; RA may have reduced subset, although no identified. Sensitivity supported robustness our findings. Conclusions existed subset while be potentially aided clinical diagnosis treatment or DLBCL.

Language: Английский

---

Influence of immune cells and inflammatory factors on Alzheimer’s disease axis: evidence from mediation Mendelian randomization study

BMC Neurology, Journal Year: 2025, Volume and Issue: 25(1)

Published: Feb. 5, 2025

Alzheimer's disease (AD) is one of the most common forms dementia in elderly, characterized by progressive neurodegeneration. While exact etiology AD remains unclear, immune inflammation known to play a significant role disease. This study utilized two-sample Mendelian randomization (MR) approach assess causal relationship between different types cells and AD, while considering inflammatory factors as intermediate variables. Data were collected from three sources: cell data (731 phenotypes), (48 cytokines 8,293 individuals), (35,274 cases, 59,163 controls). Multiple MR methods employed minimize bias, detailed descriptions instrumental variable selection statistical provided. The findings suggest potential relationships six well 13 factors. Additionally, two statistically found have with AD. Specifically, CD33-HLA DR + CD45 on may further influence regulating Interleukin-2 levels. provides valuable insights into immunoinflammatory pathogenesis offers partial guidance for development relevant interventions, thereby contributing beneficial information prevention treatment related diseases.

Language: Английский

---

Genetically determined physical activity levels, sedentary behaviours, and their association with the risk of age-related macular degeneration

Journal of International Medical Research, Journal Year: 2025, Volume and Issue: 53(2)

Published: Feb. 1, 2025

Objective To investigate the causal effects of physical activity and sedentary traits on risk Age-related macular degeneration (AMD). Methods A two-sample Mendelian randomization (MR) analysis was used to relationship between AMD. We genome-wide association studies (GWAS) summary statistics from two publicly available biobank-scale cohorts: UK Biobank FinnGen. Physical data were self-reported by 703,901 participants behaviour gathered 159,606 FinnGen participants. Our primarily inverse variance weighted (IVW) method. Result Engaging in moderate-to-vigorous significantly reduced AMD with an odds ratio 0.77 (95% CI: 0.66–0.89). However, leisure screen time showed a slight but non-statistically significant upward trend. Sedentary at work, commuting no risk. Conclusions This study MR examine activity, behaviour, It offers genetic evidence suggesting that may protect against AMD, emphasizing significance lifestyle factors maintaining ocular health.

Language: Английский

---

The association between immune cells and acute kidney injury: insights from Mendelian randomization

Renal Failure, Journal Year: 2025, Volume and Issue: 47(1)

Published: March 2, 2025

Language: Английский

---

Multicomponent Mendelian randomization and machine learning studies of potential drug targets for neurodegenerative diseases

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: April 18, 2025

Neurodegenerative diseases (NDDs) remain a global health challenge. Alzheimer's disease (AD) and Parkinson's (PD) are the main types of NDDs worldwide, Mendelian Randomization (MR) analysis across multi-omics entire genome offers novel strategies for identifying potential drug targets. This study used MR summary-based MR(SMR) to explore causal relationship between genes NDDs. Colocalization machine learning further validated reinforced findings. The pharmacological activity candidate targets was confirmed via molecular docking Molecular dynamics. revealed 14 that were closely associated with both Specifically, IQCE(AD), HDHD2(AD), COMMD10(AD), ALPP (AD), FXYD6 STK3 (PD), LHFPL2 ENPP4 identified as risk factors (OR > 1), whereas HEXIM2 TSC22D4 CHRNB1 BAG4 SLC25A1 IL15 protective < 1). results strong binding activities PREDNISOLONE(ALPP = -7.6 kcal/mol), PANCURONIUM BROMIDE(CHRNB1 -8 CHEMBL379975(STK3 =-10.7 kcal/mol) SIROLIMUS(IL15 -9 kcal/mol). dynamics simulations stable IL15-Sirolimus, ALPP-Prednisolone, STK3-CHEMBL379975, CHRNB1-Rocuronium bromide complexes. promising therapeutic NDDs, providing new insights targeted therapies clinical Our provide evidence future studies aimed at developing appropriate interventions.

Language: Английский

---

The causal relationship between immune cell traits and schizophrenia: a Mendelian randomization analysis

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 27, 2024

Introduction The complex and unresolved pathogenesis of schizophrenia has posed significant challenges to its diagnosis treatment. While recent research established a clear association between immune function schizophrenia, the causal relationship two remains elusive. Methods We employed bidirectional two-sample Mendelian randomization approach investigate 731 cell traits by utilizing public GWAS data. further validated six types white measures. Results found overall effects on were significantly higher than reverse ones (0.011 ± 0.049 vs 0.001 0.016, p &lt; 0.001), implying that disease may lead an increase in cells itself. also identified four risk schizophrenia: CD11c+ monocyte %monocyte (odds ratio (OR): 1.06, 95% confidence interval (CI): 1.03~1.09, FDR = 0.027), CD62L- (OR:1.06, CI: CD25 IgD+ CD38- naive B (OR:1.03, CI:1.01~1.06, 0.042), CD86 (OR 1.04, 0.042). However, we did not detect any traits. Using blood data, increases lymphocyte counts 95%CI: 1.01-1.04, 0.007), total (OR:1.02, 0.021) 1.00-1.03, 0.034). nominally associated with (OR:1.08,95%CI:1.01-1.16, P=0.019). Discussion Our study system is complex, enhancing our understanding role regulation development this disorder. These findings offer new insights for exploring diagnostic therapeutic options schizophrenia.

Language: Английский

---

Exploring correlations between immune cell phenotypes and the risk of epilepsy: A bidirectional Mendelian randomization study

Epilepsy & Behavior, Journal Year: 2024, Volume and Issue: 157, P. 109896 - 109896

Published: June 20, 2024

Language: Английский

---

Causal association between skin cancer and immune cells: mendelian randomization (MR) study

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 17, 2024

Abstract Background Numerous meta-analyses and clinical studies have shown that subtypes of immune cells are associated with the development skin cancer, but it is not clear whether this association causal or biased. Mendelian randomization (MR) analysis reduces effect confounding factors improves accuracy results when compared to traditional studies. Thus, in order examine relationship between various cell study employs two-sample MR. Methods This assesses 731 characteristics cancer using a Mendel methodology. Multiple MR methods were used bias derive reliable estimates causality instrumental variables outcomes. Comprehensive sensitivity analyses validate stability, heterogeneity horizontal multiplicity results. Results We discovered potential relationships different types disease. Specifically, one type as potentially malignant melanoma (MM), eight basal carcinoma (BCC), four actinic keratosis (AK), no found squamous carcinoma(SCC), stability all Conclusion demonstrates close connection disease by genetic means, which enriches current knowledge about role also contributes design therapeutic strategies from an immunological perspective.

Language: Английский

---

Causal role of gut microbiota, serum metabolites, immunophenotypes in myocarditis: a mendelian randomization study

Frontiers in Genetics, Journal Year: 2024, Volume and Issue: 15

Published: Aug. 30, 2024

The intricate relationship among gut microbiota, serum metabolites, and immunophenotypes may significantly impact myocarditis. However, direct causal links between these domains myocarditis are not well understood.

Language: Английский

---