Genetic associations between circulating immune cells and periodontitis highlight the prospect of systemic immunoregulation in periodontal care DOI Creative Commons
Xinjian Ye, Yijing Bai, Mengjun Li

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 29, 2023

Abstract Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues be an attractive approach in care, particularly within the context "predictive, preventive, personalized" periodontics. In present study, genetic proxies identified through genome-wide association studies (GWAS) for circulating immune cells periodontitis were incorporated into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable subgroup analysis, reverse Bayesian model averaging (MR-BMA) utilized investigate causal relationships. Furthermore, transcriptome-wide study (TWAS) colocalization analysis deployed pinpoint underlying genes. Consequently, MR indicated between neutrophils, natural killer T cells, plasmacytoid dendritic elevated risk periodontitis. MR-BMA revealed that neutrophils primary contributors The high-confidence genes S100A9 S100A12 , located on 1q21.3, could potentially serve as targets neutrophil-mediated These findings hold promise early diagnosis, assessment, targeted prevention, personalized treatment Considering marginal observed our further research required thoroughly comprehend biological underpinnings ascertain clinical relevance.

Language: Английский

Effect of the gut microbiome, plasma metabolome, peripheral cells, and inflammatory cytokines on obesity: a bidirectional two-sample Mendelian randomization study and mediation analysis DOI Creative Commons
Ying Li, Xin Wang, Zitong Zhang

et al.

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

Published: March 15, 2024

Background Obesity is a metabolic and chronic inflammatory disease involving genetic environmental factors. This study aimed to investigate the causal relationship among gut microbiota abundance, plasma metabolomics, peripheral cell (blood immune cell) counts, cytokines, obesity. Methods Summary statistics of 191 traits (N = 18,340), 1,400 metabolite 8,299), 128 counts cells, N 408,112; 3,757), 41 cytokine 8,293), 6 obesity were obtained from publicly available genome-wide association studies. Two-sample Mendelian randomization (MR) analysis was applied infer links using inverse variance-weighted, maximum likelihood, MR-Egger, weighted median, mode, Wald ratio methods. Several sensitivity analyses also utilized ensure reliable MR results. Finally, we used mediation identify pathway mediated by metabolites, cytokines. Results revealed effect 44 taxa, 281 27 8 cytokines on Among them, five shared taxa belonged phylum Actinobacteria , order Bifidobacteriales family Bifidobacteriaceae genus Lachnospiraceae UCG008, species Eubacterium nodatum group. Furthermore, screened 42 7 1 cytokine. Based known observed that pathways D-arginine, D-ornithine, linoleic acid, glycerophospholipid metabolism closely related 20 relationships, including obesity, 17 2 Sensitivity represented no heterogeneity or pleiotropy in this study. Conclusion Our findings support microbiota, These biomarkers provide new insights into mechanisms underlying contribute its prevention, diagnosis, treatment.

Language: Английский

Citations

12
Genetic associations between circulating immune cells and periodontitis highlight the prospect of systemic immunoregulation in periodontal care DOI Creative Commons
Xinjian Ye, Yijing Bai, Mengjun Li

et al.

eLife, Journal Year: 2024, Volume and Issue: 12

Published: March 27, 2024

Periodontitis drives irreversible destruction of periodontal tissue and is prone to exacerbating inflammatory disorders. Systemic immunomodulatory management continues be an attractive approach in care, particularly within the context ‘predictive, preventive, personalized’ periodontics. The present study incorporated genetic proxies identified through genome-wide association studies for circulating immune cells periodontitis into a comprehensive Mendelian randomization (MR) framework. Univariable MR, multivariable subgroup analysis, reverse Bayesian model averaging (MR-BMA) were utilized investigate causal relationships. Furthermore, transcriptome-wide colocalization analysis deployed pinpoint underlying genes. Consequently, MR indicated between neutrophils, natural killer T cells, plasmacytoid dendritic elevated risk periodontitis. MR-BMA revealed that neutrophils primary contributors high-confidence genes S100A9 S100A12 , located on 1q21.3, could potentially serve as targets neutrophil-mediated These findings hold promise early diagnosis, assessment, targeted prevention, personalized treatment Considering marginal observed our study, further research required comprehend biological underpinnings ascertain clinical relevance thoroughly.

Language: Английский

Citations

8
Causal relationship between diabetes and depression: A bidirectional Mendelian randomization study DOI
Zhe Wang, Zhiqiang Du, Rongrong Lu

et al.

Journal of Affective Disorders, Journal Year: 2024, Volume and Issue: 351, P. 956 - 961

Published: Feb. 12, 2024

Language: Английский

Citations

5
Obesity and periodontitis: a comprehensive review of their interconnected pathophysiology and clinical implications DOI Creative Commons
Claudia Reytor-González, Juan Marcos Parise-Vasco,

N Llobregat Gonzalez

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: Aug. 7, 2024

Obesity and periodontitis are significant health problems with a complex bidirectional relationship. Excess body fat is linked to systemic diseases can lead persistent inflammation, potentially harming periodontal health. Periodontitis, chronic inflammatory condition affecting the supporting structures of teeth, poses substantial risks. Both conditions share pathological processes such as inflammation oxidative stress, which aggravate status make treatment more challenging. Understanding this interaction crucial for developing effective management strategies both diseases. This study explores multifaceted aspects obesity their reciprocal

Language: Английский

Citations

4
Causal genes identification of giant cell arteritis in CD4+ Memory t cells: an integration of multi-omics and expression quantitative trait locus analysis DOI Creative Commons

Qiyi Yu,

Yifan Wu, Xianda Ma

et al.

Inflammation Research, Journal Year: 2025, Volume and Issue: 74(1)

Published: Jan. 7, 2025

Abstract Background Giant cell arteritis (GCA) is a prevalent artery and strongly correlated with age. The role of CD4+ Memory T cells in giant has not been elucidated. Method Through single-cell analysis, we focused on the arteritis. eQTL analysis mendelian randomization identified significant genes which have causal effect risk. were subsequently divided into gene-positive gene-negative groups, then further was conducted. Mendelian plasma proteins, blood-urine biomarkers metabolites also performed. Eventually, PMA induced Jurkat lines used for biological experiments to explore specific functions cells. Results Similarity GCA old samples explored. DDIT4 ARHGAP15 as risk via randomization. ± or indicated differences aspects involving intercellular communication, functional pathways, protein activity, metabolism drug sensitivity between positive negative groups. In vitro experiments, including overexpression knockdown, demonstrated that leading chronic, low-intensity inflammatory state cells, eventually promoting development GCA. Conclusion effects Specifically, exhibit pro-inflammatory promotes cell.

Language: Английский

Citations

0
Identification and validation of transcriptome-wide association study-derived genes as potential druggable targets for osteoarthritis DOI Creative Commons
Xindie Zhou, Xinjian Ye, Jiapei Yao

et al.

Bone and Joint Research, Journal Year: 2025, Volume and Issue: 14(3), P. 224 - 235

Published: March 13, 2025

Aims Osteoarthritis (OA) is a widespread chronic degenerative joint disease with an increasing global impact. The pathogenesis of OA involves complex interactions between genetic and environmental factors. Despite this, the specific mechanisms underlying remain only partially understood, hindering development targeted therapeutic strategies. Methods A transcriptome-wide association study (TWAS) was conducted for site-specific phenotypes using functional summary-based imputation (FUSION). High-confidence candidate genes were identified through rigorous quality control measures, including joint/conditional analysis, permutation tests, best model evaluation, colocalization analysis. Co-expression network analysis performed to elucidate biology these genes. Druggable gene targets their structural models retrieved from DrugBank SWISS-MODEL databases. Finally, enrichment mitogen-activated protein kinase 3 ( MAPK3 ) SMAD3 in validated biochemically vitro vivo models, as well human histological sections. Results Utilizing FUSION algorithm, TWAS 794 OA. After control, 14 classified high-confidence genes, seven recognized potential drug GCAT, MAPK3, MST1R, PFKM, RAD9A, SMAD3, USAP8 . revealed strong biological Both experiments demonstrated high activity enriched expression two Conclusion present tissue-specific druggable OA, providing new insights into landscape processes involved Further studies are warranted confirm findings. Cite this article: Bone Joint Res 2025;14(3):224–235.

Language: Английский

Citations

0
Exploring the causal association between genetically determined circulating metabolome and hemorrhagic stroke DOI Creative Commons
Yaolou Wang, Yingjie Shen, Qi Li

et al.

Frontiers in Nutrition, Journal Year: 2024, Volume and Issue: 11

Published: May 15, 2024

Background Hemorrhagic stroke (HS), a leading cause of death and disability worldwide, has not been clarified in terms the underlying biomolecular mechanisms its development. Circulating metabolites have closely associated with HS recent years. Therefore, we explored causal association between circulating metabolomes using Mendelian randomization (MR) analysis identified molecular effects. Methods We assessed relationship serum (CSMs) bidirectional two-sample MR method supplemented five ways: weighted median, Egger, simple mode, MR-PRESSO. The Cochran Q-test, MR-Egger intercept test, MR-PRESSO served for sensitivity analyses. Steiger test reverse were used to estimate causality. Metabolic pathway analyses performed MetaboAnalyst 5.0, genetic effects by linkage disequilibrium score regression. Significant further synthesized meta-analysis, multivariate correct common confounders. Results finally recognized four metabolites, biliverdin (OR 0.62, 95% CI 0.40–0.96, P MVMR = 0.030), linoleate (18. 2n6) 0.20, 0.08–0.54, 0.001),1-eicosadienoylglycerophosphocholine* 2.21, 1.02–4.76, 0.044),7-alpha-hydroxy-3 -oxo-4-cholestenoate (7-Hoca) 0.27, 0.09–0.77, 0.015) significant relation HS. Conclusion demonstrated associations hemorrhagic stroke. Monitoring, diagnosis, treatment might be valuable approach.

Language: Английский

Citations

3
Appraising the life‐course impact of Epstein‐Barr virus exposure and its genetic signature on periodontitis DOI
Xinjian Ye, Yuan Jian, Yijing Bai

et al.

Journal of Periodontology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 4, 2024

Abstract Background Periodontitis arises from a multifaceted interplay of environmental variables and genetic susceptibility, where microbial infection plays an indispensable part. Epstein‐Barr virus (EBV) exposure has long been considered associated with periodontitis activity; however, the causal relationship connection between them remain unknown. Methods Within life‐course context, our study employed comprehensive Mendelian randomization (MR) methods, including univariable, multivariable, Bayesian model averaging, reverse MR, to investigate association EBV periodontitis. Additionally, linkage disequilibrium score regression colocalization analysis were utilized assess cross‐trait correlations, followed by transcriptome‐wide enrichment discern genetic‐phenotypic biological profiles. Results Heightened levels antibodies, particularly early antigen diffuses (which serve as indicators or reactivation), are increased risk (odds ratio [OR]: 1.27 [1.09–1.47], p = 6.05 × 10 −3 ) demonstrate significant correlation ( 4.11 ). This pathogenesis may involve high‐confidence gene RNASEK located in 17p13.1. Genetically predicted early‐life anti‐EBV immunoglobulin G (IgG) correlated reduced (OR: 0.89 [0.82–0.97], 1.76 Conclusions The present highlights impact its hallmark on periodontitis, providing novel perspectives into underlying management strategies for EBV‐related These findings underscore diverse clinical public health implications, encompassing antiviral therapies, viral vaccination strategies, tailored interventions individualized management. Further research is required validate expand upon findings. Plain Language Summary chronic inflammatory disease driven interactions pathogens host immune system. While bacteria have traditionally focus research, recent studies highlight significance virus‐bacteria interactions, role (EBV)—a herpesvirus infecting over 90% global population—in development However, mechanisms unclear. Our genome‐wide multi‐omics approaches link We found that reactivation increases whereas exposure, possibly enabling resistance, reduce it. Essential genes identified potential mediators, CRTC3‐AS1 , HLA‐DQA1 . provide insights EBV‐periodontitis connection. For example, testing control could benefit patients unresponsive standard bacterial treatments, via might elucidate these contribution interactions.

Language: Английский

Citations

3
Causal effects of circulating inflammatory proteins on oral phenotypes: Deciphering immune-mediated profiles in the host-oral axis DOI
Xinjian Ye, Chen Tan, Jianhua Cheng

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 144, P. 113642 - 113642

Published: Nov. 22, 2024

Language: Английский

Citations

3
Causal associations between gut microbiota and primary biliary cholangitis: a bidirectional two-sample Mendelian randomization study DOI Creative Commons
Jiahao Zhang,

Gefeng Wu,

Yuhong Tang

et al.

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 15, 2023

Background Previous studies have suggested an association between gut microbiota and primary biliary cholangitis (PBC). Nonetheless, the causal relationship PBC risk remains unclear. Methods A bidirectional two-sample Mendelian Randomization (MR) study was employed using summary statistical data for from MiBioGen consortium Genome-Wide Association Studies (GWAS) database to investigate relationships 211 risk. Inverse variance weighted (IVW) method analytical approach assess causality, pleiotropy heterogeneity tests were verify robustness of findings. Additionally, we performed reverse MR analyses possibility association. Results The IVW identified five that demonstrated associations with PBC. Order Selenomonadales [odds ratio (OR) 2.13, 95% confidence interval (CI) 1.10–4.14, p = 0.03], Bifidobacteriales (OR 1.58, CI 1.07–2.33, 0.02), Genus Lachnospiraceae_UCG_004 1.64, 95%CI 1.06–2.55, 0.03) correlated a higher PBC, while Family Peptostreptococcaceae 0.65, 0.43–0.98, 0.04) Ruminococcaceae 0.33, 0.15–0.72, 0.01) had protective effect on analysis no statistically significant these specific microbial taxa. Conclusion This revealed there taxa which may provide novel perspectives theoretical basis clinical prevention, diagnosis, treatment

Language: Английский

Citations

7