Causal Association between Periodontitis and Parkinson’s Disease: A Bidirectional Mendelian Randomization Study

Botelho, João; Machado, Vanessa; Mendes, José João; Mascarenhas, Paulo

doi:10.3390/genes12050772

Cited by 15 publications

(17 citation statements)

References 41 publications

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“…To explore causality in this bidirectional association, some researchers have used two-sample Mendelian randomization (MR) in European ancestry populations. However, the MR study found no bidirectional causal genetic predisposition between periodontitis and PD ( Botelho et al, 2021 ). Surprisingly, some studies using population-based retrospectively matched cohorts have found that patients with periodontitis are at a higher risk of developing PD ( Chen et al, 2017 ).…”

Section: Discussionmentioning

confidence: 98%

Bioinformatics analysis of gene expression profile and functional analysis in periodontitis and Parkinson’s disease

Shi

et al. 2022

Front. Aging Neurosci.

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Periodontitis is a chronic inflammatory disease inextricably linked to both the innate and acquired immune systems of the body. Parkinson’s disease (PD) is a neurodegenerative disease caused by immune system dysfunction. Although recent studies suggest that a clinical relationship exists between PD and periodontitis, the pathogenesis of this relationship is unclear. Therefore, in the present study, we obtained datasets of periodontitis and PD from the Gene Expression Omnibus (GEO) database and extracted 785 differentially expressed genes (DEGs), including 15 common upregulated genes and four common downregulated genes. We performed enrichment analyses of these DEGs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses. We found that the genes were mainly enriched in keratinocyte differentiation, neuronal cell bodies, and structural constituents of epidermis terms, and pathways such as immune response and synaptic pathways. In addition, we screened matching hub genes by constructing a protein–protein interaction (PPI) network map and a Molecular Complex Detection (MCODE) map using the Cytoscape software. The hub genes were then subjected to GO enrichment analysis, which revealed that the dopamine biosynthetic process, dopaminergic synapse and dopamine-binding terms, and dopaminergic synapse and serotonergic synapse pathways were primarily where they were expressed. Finally, we selected four of these genes for validation in the periodontitis and PD datasets, and we confirmed that these hub genes were highly sensitive and specific for diagnosing and monitoring PD and periodontitis. In conclusion, the above experimental results indicate that periodontitis is a high-risk factor for PD, and the association between these two conditions is mainly manifested in immune and dopamine-related pathways. Hub genes, such as the CDSN, TH, DDC, and SLC6A3 genes, may serve as potential biomarkers for diagnosing or detecting PD.

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Section: Discussionmentioning

confidence: 98%

Bioinformatics analysis of gene expression profile and functional analysis in periodontitis and Parkinson’s disease

Shi

et al. 2022

Front. Aging Neurosci.

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“…Additionally, F-statistics and the proportion of phenotypic variation explained (PVE) were computed for each IV, serving as measures of IV strength and safeguards against instrumental bias. SNPs with an F-statistic less than 10 were identi ed as weak instruments and consequently excluded from the instrumental variable set (22).…”

Section: Selection Of Instrumental Variables (Ivs)mentioning

confidence: 99%

Uncovering Causal Associations of Immune Cells with Rheumatoid Arthritis: A Mendelian Randomization Study

王,

Su,

Zhang

et al. 2024

Preprint

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Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by progressive joint damage and functional limitations, often accompanied by comorbidities. While the impact of immune cells on the development of RA is recognized, the precise causal relationships with various immunophenotypes are yet to be fully understood. Methods We performed a comprehensive two-sample Mendelian randomization (MR) study to explore the associations between immunophenotypes and RA. Utilizing publicly available genetic datasets, we examined causal links involving 731 immune cell traits, categorized into four groups: relative cell counts (RC), median fluorescence intensities (MFI), morphological parameters (MP), and absolute cell counts (AC). Extensive sensitivity analyses were carried out to validate the robustness of our results. These analyses aimed to assess heterogeneity and investigate the potential influence of horizontal pleiotropy. Results After applying FDR correction, two specific immunophenotypes were found to be associated with RA: CD33dim HLA-DR + CD11b+ %CD33dim HLA-DR + and CD33dimHLA-DR + CD11b-%CD33dimHLA-DR+. The odds ratios (ORs) for RA risk forthese immunophenotypes, calculated using the inverse variance weighting(IVW) method, were 0.970 (95% CI = 0.955–0.985, P = 1.09×10− 4, PFDR = 0.058) and 1.027 (95% CI = 1.011–1.042, P = 5.05×10− 4, PFDR = 0.074), respectively. In contrast, without FDR correction, six additional immunophenotypes showed significant associations with RA: CD14 on CD33dim HLA-DR + CD11b+, CD16 on CD14 + CD16 + monocytes, CD11b on basophils, CD3 on TD CD4+, PDL-1 on CD14- CD16 + monocytes, and CD4 on HLA-DR + CD4+. Of these, the first two were linked to increased RA risk, while the latter four exhibited protective characteristics. Conclusions This study highlights a strong genetic link between immune cell profiles and RA, illuminating potential targets for innovative therapeutic strategies.

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“…MR uses an instrumental variable (IV) to further analyze the causal relationship between samples [14]. These IVs in MR must meet three assumptions: (1) correlation hypothesis: strong correlation with exposure; (2) exclusivity hypothesis: it has nothing to do with the outcome; (3) independence hypothesis: it has nothing to do with confounding factors [15,16]. Figure 1 shows a schematic of the Mendelian randomization study of periodontitis and breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Association between periodontitis and breast cancer: two-sample Mendelian randomization study

et al. 2023

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Objectives The purpose of this study was to investigate whether there is a causal relationship between periodontitis and breast cancer by Mendelian randomization analysis. Materials and methods We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied complementary methods, including weighted median, weighted mode, simple mode, MR-Egger regression, and MR-pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy. Results IVW MR analysis showed no effect of periodontitis on breast cancer (IVW OR=0.99, P =0.14). Similarly, no significant causal relationship between breast cancer and periodontitis was found in reverse MR analysis (IVW OR=0.95, P =0.83). The results of MR-Egger regression, weighted median, and weighted mode methods were consistent with those of the IVW method. Based on sensitivity analyses, horizontal pleiotropy is unlikely to distort causal estimates. Conclusions Although observational studies have reported an association between periodontitis and breast cancer, the results of our MR analysis do not support a causal relationship between periodontitis and breast cancer. Clinical relevance Mendelian randomization study can more clearly analyze the causal relationship between periodontitis and breast cancer, in order to provide a certain reference for clinicians and deepen the understanding of the relationship between periodontitis and breast cancer, to explore more possible associations between periodontitis and systemic diseases.

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Causal Association between Periodontitis and Parkinson’s Disease: A Bidirectional Mendelian Randomization Study

Cited by 15 publications

References 41 publications

Bioinformatics analysis of gene expression profile and functional analysis in periodontitis and Parkinson’s disease

Bioinformatics analysis of gene expression profile and functional analysis in periodontitis and Parkinson’s disease

Uncovering Causal Associations of Immune Cells with Rheumatoid Arthritis: A Mendelian Randomization Study

Association between periodontitis and breast cancer: two-sample Mendelian randomization study

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