Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study

Tang, Yanjuan; Liu, Weizhi; Kong, Weishuang; Zhang, Shuangyi; Zhu, Tao

doi:10.3389/fimmu.2023.1077088

Cited by 9 publications

(9 citation statements)

References 53 publications

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“…The directionality of pleiotropy can be detected and adjusted using the MR-Egger technique based on the Instrument Strength Independent of Direct Effect (InSIDE) assumption, although it is underpowered ( 39 ). Additionally, the MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test was used to detect potential horizontal pleiotropy and reduce the effects of pleiotropy by eliminating outliers ( 40 ). The heterogeneity was assessed using Cochran's Q-statistic.…”

Section: Methodsmentioning

confidence: 99%

Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study

Tang,

Xu,

Zhang

et al. 2023

Front. Nutr.

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BackgroundAlthough well-documented, the causal relationships between diet-derived circulating antioxidants, oxidative stress, and osteoarthritis (OA) are equivocal. The objective of this study is to employ two-sample Mendelian randomization (MR) to investigate possible causal relationships among dietary-derived circulating antioxidants, oxidative stress damage indicators, and OA risk.MethodsSingle-nucleotide polymorphisms for diet-derived circulating antioxidants (ascorbate, β-carotene, lycopene, retinol, and α-and γ-tocopherol), assessed as absolute levels and metabolites, as well as oxidative stress injury biomarkers (GSH, GPX, CAT, SOD, albumin, and total bilirubin), were retrieved from the published data and were used as genetic instrumental variables. Summary statistics for gene–OA associations were obtained from publicly available and two relatively large-scale GWAS meta-analyses to date. The inverse-variance weighting method was utilized as the primary MR analysis. Moreover, multivariable MR was used to determine if mediators (BMI and smoking) causally mediated any connection. Furthermore, for each exposure, MR analyses were conducted per outcome database and then meta-analyzed.ResultsGenetically predicted absolute retinol level was causally associated with hip OA risk [odds ratios (ORs) = 0.40, 95% confidence interval (CI) = 0.24–0.68, FDR-corrected p = 0.042]. Moreover, genetically predicted albumin level was causally associated with total OA risk (OR = 0.80, 95% CI = 0.75–0.86, FDR-corrected p = 2.20E-11), as well as the risk of hip OA (OR = 0.75, 95% CI = 0.68–0.84, FDR-corrected p = 1.38E-06) and knee OA (OR = 0.82, 95% CI = 0.76–0.89, FDR-corrected p = 4.49E-06). In addition, MVMR confirmed that the effect of albumin on hip OA is independent of smoking initiation, alcoholic drinks per week, and moderate-to-vigorous physical activity levels but may be influenced by BMI.ConclusionEvidence from our study supports a potentially protective effect of high levels of retinol and albumin on OA risk.

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Section: Methodsmentioning

confidence: 99%

Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study

Tang,

Xu,

Zhang

et al. 2023

Front. Nutr.

Self Cite

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“…Eiris et al (158) showed a significant association between three SNPs (rs6887695, rs3212227 and rs2201841) and diabetes mellitus. Recent GWAS findings have indicated a genetic association between psoriasis and autoimmune diseases (such as multiple sclerosis, rheumatoid arthritis and autoimmune hypothyroidism), neuromuscular diseases (including Alzheimer's and Parkinson's diseases) (159)(160)(161)(162), chronic inflammation (163) and skin diseases (164). Future investigations will aim to conduct a transdisease meta-analysis and Mendelian randomization to determine the causal relationship between psoriasis and the aforementioned diseases.…”

Section: Discussionmentioning

confidence: 99%

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Yang,

Liu,

et al. 2024

Mol Med Rep

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Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome-wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)-R software and chi-square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome-wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5×10 −8 , located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA-A*02:07 and HLA-C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta-analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

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“…Following a rigorous surveillance, we narrowed our selection to 7 separate SNPs for GERD and 28 SNPs for CWP. To do this, we eliminated chain imbalances and associated confounders, with smoking being recognized as a risk factor for GERD and smoking, obesity, mental illness, cancer, and osteoarthritis as risk factors for CWP (27)(28)(29). Furthermore, SNPs that did not appear in the endpoint GWAS were deleted.…”

Section: Genetic Instrumental Variablesmentioning

confidence: 99%

The causal correlation between gastroesophageal reflux disease and chronic widespread pain: a bidirectional mendelian randomization study

Chen,

Tu,

Zhou

et al. 2024

Preprint

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Background: Previous observational research found a relationship between gastroesophageal reflux disease (GERD) and chronic widespread pain (CWP). Despite this, it is unknown which, if any, of the conditions produces the other. Our study will use bidirectional Mendelian randomization (MR) to evaluate their causal link. Methods: We examined two sets of publically accessible data from genome-wide association studies (GWAS): GERD (129,080 cases and 602,604 controls) and CWP (6,914 cases and 242,929 controls). We used the inverse variance weighting (IVW) approach as the major analysis method, but we also ran weighted median and MR-Egger regression analyses. We performed various sensitivity studies to assess the conclusions' consistency, horizontal pleiotropy, and stability. Results: MR analysis showed that CWP increased the risk of developing GERD [NSNP = 4, odds ratio (OR): 245.244; 95% confidence interval (CI): 4.35E+00,1.38E+04; p = 0.007 < 0.05] and vice versa (NSNP = 28; OR:1.019; 95% CI: 1.009-1.029; p = 0.029 < 0.05). Bidirectional evidence of causality existed. The sensitivity analysis demonstrated the robustness and reliability of the findings. Conclusions: Our study demonstrated a bidirectional causal relationship between GERD and chronic widespread pain, and future interventions for CWP may be an effective strategy for preventing or mitigating GERD and vice versa.

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Multisite chronic pain and the risk of autoimmune diseases: A Mendelian randomization study

Cited by 9 publications

References 53 publications

Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study

Genetic liability for diet-derived circulating antioxidants, oxidative stress, and risk of osteoarthritis: a Mendelian randomization study

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

The causal correlation between gastroesophageal reflux disease and chronic widespread pain: a bidirectional mendelian randomization study

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