No Genetic Causal Association Between Periodontitis and Arthritis: A Bidirectional Two-Sample Mendelian Randomization Analysis

Yin, Kang-Jia; Huang, Jianguo; Wang, Peng; Yang, Xiao‐Ke; Tao, Sha‐Sha; Li, Hong‐Miao; Ni, Jiazuan; Pan, Hai‐Feng

doi:10.3389/fimmu.2022.808832

Cited by 67 publications

(58 citation statements)

References 59 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The random effects IVW method was the primary method. The random effects IVW method uses a meta-analytical approach to combine the Wald ratios for the causal effects of each SNP and can provide the most precise estimates when all selected IVs are valid [ 31 , 32 ]. The weighted median method can provide a suitable causal assessment even if more than 50% of the IVs are ineffective [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

Does Having Rheumatoid Arthritis Increase the Dose of Depression Medications? A Mendelian Randomization Study

Wan

Xie

Yang

et al. 2023

JCM

View full text Add to dashboard Cite

Background: Rheumatoid arthritis (RA) increases the risk of depression. However, studies on the effects of RA on the dose of depression medications are limited. Therefore, in this study, we used two-sample Mendelian randomization (MR) to explore whether RA increases the dose of depression medications and gain a more comprehensive understanding of the relationship between RA and depression. Methods: Two-sample MR was used to evaluate the causal effect of RA on the dose of depression medications. The aggregated data on RA originated from extensive genome-wide association studies (GWASs) of European descent (14,361 cases and 42,923 controls). The summary GWAS data for the dose of depression medications were derived from the FinnGen consortium (58,842 cases and 59,827 controls). Random effects inverse-variance weighted (IVW), MR-Egger regression, weighted median, and fixed effects IVW methods were used for the MR analysis. Random effects IVW was the primary method. The heterogeneity of the MR results was detected using the IVW Cochran’s Q test. The pleiotropy of the MR results was detected using MR-Egger regression and the MR pleiotropy residual sum and outlier (MR-PRESSO) test. Finally, a leave-one-out analysis was performed to determine whether the MR results were affected by a specific single-nucleotide polymorphism (SNP). Results: The primary method, random effects IVW, revealed that genetically predicted RA had a positive causal association with the dose of depression medications (Beta, 0.035; 95% confidence interval (CI), 0.007–0.064; p = 0.015). The IVW Cochran’s Q test results revealed no heterogeneity in the MR analysis (p > 0.05). The MR-Egger regression and MR-PRESSO tests revealed that there was no pleiotropy in our MR analysis. The leave-one-out analysis confirmed that a single SNP did not affect the MR results, indicating the study’s robustness. Conclusion: Using MR techniques, we discovered that having RA increases the dose of depression medications; however, the exact mechanisms and pathways still need to be further explored.

show abstract

Section: Methodsmentioning

confidence: 99%

Does Having Rheumatoid Arthritis Increase the Dose of Depression Medications? A Mendelian Randomization Study

Wan

Xie

Yang

et al. 2023

JCM

View full text Add to dashboard Cite

show abstract

“…We further performed an MR analysis on gut microbes that were found to be genetically related to DVT. Three assumptions of MR must be met to obtain impartial results: (1) the genetic IVs should have a strong link to the exposure; (2) the genetic IVs are not associated with confounders linked to the chosen exposure and outcome; and (3) genetic IVs influence the outcome only through exposure and not via other biological pathways ( 39 ).…”

Section: Methodsmentioning

confidence: 99%

Large-scale correlation analysis of deep venous thrombosis and gut microbiota

Yang

Luo

Zhang

et al. 2022

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

ObjectiveAlthough previous studies have shown that gut microbiota may be involved in the occurrence of deep venous thrombosis (DVT), the specific link between the two remains unclear. The present study aimed to explore this question from a genetic perspective.Materials and methodsGenome-wide association study (GWAS) summary data of DVT were obtained from the UK Biobank (N = 9,059). GWAS summary data of the gut microbiota were obtained from the Flemish Gut Flora Project (N = 2,223) and two German cohorts (FoCus, N = 950; PopGen, N = 717). All the participants were of European ancestry. Linkage disequilibrium score (LDSC) regression has great potential for analyzing the heritability of disease or character traits. LDSC regression was used to analyze the genetic correlation between DVT and the gut microbiota based on the GWAS summary data obtained from previous studies. Mendelian randomization (MR) was used to analyze the genetic causal relationship between DVT and the gut microbiota. We used the random effects inverse variance weighted, MR Egger, weighted median, simple mode, and weighted mode to perform MR analysis. We performed a sensitivity analysis of the MR analysis results by examining heterogeneity and horizontal pleiotropy.ResultsLinkage disequilibrium score analysis showed that Streptococcaceae (correlation coefficient = −0.542, SE = 0.237, P = 0.022), Dialister (correlation coefficient = −0.623, SE = 0.316, P = 0.049), Streptococcus (correlation coefficient = −0.576, SE = 0.264, P = 0.029), and Lactobacillales (correlation coefficient = −0.484, SE = 0.237, P = 0.042) had suggestive genetic correlation with DVT. In addition, the MR analysis showed that Streptococcaceae had a positive genetic causal relationship with DVT (P = 0.027, OR = 1.005). There was no heterogeneity or horizontal pleiotropy in the MR analysis (P > 0.05).ConclusionIn this study, four gut microbes (Streptococcaceae, Dialister Streptococcus, Lactobacillales) had suggestive genetic correlations with DVT, and Streptococcaceae had a positive causal relationship with DVT. Our findings provide a new research direction for the further study of and prevention of DVT.

show abstract

“…Then, to exclude SNPs with strong linkage disequilibrium, we performed an aggregation process (R2<0.001) ( 28 ). Finally, to ensure that the effect alleles belonged to the same allele, we adjusted the exposure and outcome datasets to eliminate ambiguous SNPs with inconsistent alleles and SNPs with intermediate allele frequencies ( 29 ).…”

Section: Methodsmentioning

confidence: 99%

The causal relationship between obesity and skin and soft tissue infections: A two-sample Mendelian randomization study

Mei

et al. 2022

Front. Endocrinol.

View full text Add to dashboard Cite

ObjectiveMany observational studies have shown that obesity strongly affects skin and soft tissue infections (SSTIs). However, whether a causal genetic relationship exists between obesity and SSTIs is unclear.MethodsA two-sample Mendelian randomization (MR) study was used to explore whether obesity is causally associated with SSTIs using a publicly released genome-wide association study (GWAS). An inverse-variance weighted (IVW) analysis was used as the primary analysis, and the results are reported as the odds ratios (ORs). Heterogeneity was tested using Cochran’s Q test and the I2 statistic, and horizontal pleiotropy was tested using the MR−Egger intercept and MR pleiotropy residual sum and outlier (MR-PRESSO).ResultsThe results of the MR analysis showed a positive effect of BMI on SSTIs (OR 1.544, 95% CI 1.399-1.704, P= 5.86 × 10-18). After adjusting for the effect of type 2 diabetes (T2D) and peripheral vascular disease (PVD), the positive effect still existed. Then, we further assessed the effect of BMI on different types of SSTIs. The results showed that BMI caused an increased risk of impetigo, cutaneous abscess, furuncle and carbuncle, cellulitis, pilonidal cyst, and other local infections of skin and subcutaneous tissues, except for acute lymphadenitis. However, the associations disappeared after adjusting for the effect of T2D and PVD, and the associations between BMI and impetigo or cellulitis disappeared. Finally, we assessed the effects of several obesity-related characteristics on SSTIs. Waist circumference, hip circumference, body fat percentage, and whole-body fat mass, excluding waist-to-hip ratio, had a causal effect on an increased risk of SSTIs. However, the associations disappeared after adjusting for the effect of BMI.ConclusionThis study found that obesity had a positive causal effect on SSTIs. Reasonable weight control is a possible way to reduce the occurrence of SSTIs, especially in patients undergoing surgery.

show abstract

No Genetic Causal Association Between Periodontitis and Arthritis: A Bidirectional Two-Sample Mendelian Randomization Analysis

Cited by 67 publications

References 59 publications

Does Having Rheumatoid Arthritis Increase the Dose of Depression Medications? A Mendelian Randomization Study

Does Having Rheumatoid Arthritis Increase the Dose of Depression Medications? A Mendelian Randomization Study

Large-scale correlation analysis of deep venous thrombosis and gut microbiota

The causal relationship between obesity and skin and soft tissue infections: A two-sample Mendelian randomization study

Contact Info

Product

Resources

About