Causal relationships between circulating inflammatory factors and IgA vasculitis: a bidirectional Mendelian randomization study

Qin, Jiading; Zhang, Ling; Ke, Bo; Liu, Tingting; Kong, Chunfang; Jin, Chenghao

doi:10.3389/fimmu.2023.1248325

Cited by 5 publications

(1 citation statement)

References 74 publications

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“…However, for certain in ammatory cytokines, where the number of identi ed SNPs was limited, we adopted a slightly relaxed p-value threshold of p < 1 × 10 − 5 for the cytokine data. This decision aimed to broaden the scope of our correlation analysis [33]. To ensure the independence of the selected SNPs, we conducted a linkage disequilibrium analysis (LD) using data from the European cohort of the 1000 Genomes Project.…”

Section: Selection Of Instruments Variablesmentioning

confidence: 99%

Genome-wide Mendelian Randomization analysis reveals specific inflammatory traits as causal risk factors for oral cancer

Zhang,

Peng

2024

Preprint

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Purpose Previous research has suggested a potential connection between persistent inflammation and the risk of developing oral cancer. However, the causal relationships between inflammatory traits and oral cancer are not yet fully understood. Methods To delve deeper into this inquiry, we implemented a two-sample Mendelian randomization (MR) analysis, utilizing genetic data from previous genome-wide association studies (GWAS). In this analysis, we explored several inflammatory traits as potential exposures, while considering oral cancer as the outcome. To ensure the robustness of our findings, we employed the inverse variance weighted (IVW) method as the primary analytical approach, alongside tests for pleiotropy and heterogeneity. Results The IVW method identified two immune-mediated inflammatory diseases that showed associations with an increased risk of oral cancer. In particular, inflammatory bowel disease was found to be correlated with a higher risk of oral cancer (p < 0.001), as well as its subtypes such as Crohn's disease (p = 0.026). Additionally, elevated levels of Interleukin-10 (IL-10) were found to be potentially associated with an increased risk of oral cancer (p = 0.048), while higher levels of IL-18 showed a protective effect on oral cancer (p = 0.011). Conclusion The results of this study offer compelling evidence supporting a causal link between distinct inflammatory traits and the susceptibility to oral cancer. These findings hold significant implications for the clinical management of oral cancer, spanning various aspects such as prevention, diagnosis, and treatment strategies.

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Section: Selection Of Instruments Variablesmentioning

confidence: 99%

Genome-wide Mendelian Randomization analysis reveals specific inflammatory traits as causal risk factors for oral cancer

Zhang,

Peng

2024

Preprint

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Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers

Bajželj,

Hladnik,

Blagus

et al. 2024

Arthritis Res Ther

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Introduction Immunoglobulin A vasculitis (IgAV) in adults has a variable disease course, with patients often developing gastrointestinal and renal involvement and thus contributing to higher mortality. Due to understudied molecular mechanisms in IgAV currently used biomarkers for IgAV visceral involvement are largely lacking. Our aim was to search for potential serum biomarkers based on the skin transcriptomic signature. Methods RNA sequencing analysis was conducted on skin biopsies collected from 6 treatment-naïve patients (3 skin only and 3 renal involvement) and 3 healthy controls (HC) to get insight into deregulated processes at the transcriptomic level. 15 analytes were selected and measured based on the transcriptome analysis (adiponectin, lipopolysaccharide binding protein (LBP), matrix metalloproteinase-1 (MMP1), C-C motif chemokine ligand (CCL) 19, kallikrein-5, CCL3, leptin, C-X-C motif chemokine ligand (CXCL) 5, osteopontin, interleukin (IL)-15, CXCL10, angiopoietin-like 4 (ANGPTL4), SERPIN A12/vaspin, IL-18 and fatty acid-binding protein 4 (FABP4)) in sera of 59 IgAV and 22 HC. Machine learning was used to assess the ability of the analytes to predict IgAV and its organ involvement. Results Based on the gene expression levels in the skin, we were able to differentiate between IgAV patients and HC using principal component analysis (PCA) and a sample-to-sample distance matrix. Differential expression analysis revealed 49 differentially expressed genes (DEGs) in all IgAV patient’s vs. HC. Patients with renal involvement had more DEGs than patients with skin involvement only (507 vs. 46 DEGs) as compared to HC, suggesting different skin signatures. Major dysregulated processes in patients with renal involvement were lipid metabolism, acute inflammatory response, and extracellular matrix (ECM)-related processes. 11 of 15 analytes selected based on affected processes in IgAV skin (osteopontin, LBP, ANGPTL4, IL-15, FABP4, CCL19, kallikrein-5, CCL3, leptin, IL-18 and MMP1) were significantly higher (p-adj < 0.05) in IgAV serum as compared to HC. Prediction models utilizing measured analytes showed high potential for predicting adult IgAV. Conclusion Skin transcriptomic data revealed deregulations in lipid metabolism and acute inflammatory response, reflected also in serum analyte measurements. LBP, among others, could serve as a potential biomarker of renal complications, while adiponectin and CXCL10 could indicate gastrointestinal involvement.

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Causal Relationship Between Systemic Circulatory Inflammatory Regulators and Intervertebral Disc Degeneration: A Bidirectional Two-Sample Mendelian Randomization Study

Chen,

Xu,

Huang

et al. 2023

Preprint

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Background In the context of the development of Intervertebral Disc Degeneration (IDD), inflammatory mediators play a pivotal role. Nevertheless, due to the influence of the inflammatory microenvironment, the causal relationship between specific inflammatory mediators and the development of IDD remains uncertain. Methods We utilized genetic data concerning systemic circulating inflammatory regulators obtained from a Genome-Wide Association Study (GWAS) analyzing 41 serum cytokines in a cohort of 8,293 individuals from Finland. The genetic data for IDD was derived from the most recent Genome-Wide Association Study summary statistics conducted within the FinnGen consortium, encompassing 37,636 IDD cases and 270,964 controls. Our analysis employed bidirectional two-sample Mendelian randomization (MR) techniques, which included several MR methods such as MR Egger, weighted median, inverse variance weighted (IVW), weighted mode, and simple mode. Additionally, the MR-PRESSO method was employed to identify horizontal pleiotropy, heterogeneity was quantified using the Cochran Q statistic, and MR Egger intercept analysis was performed to assess pleiotropy. Results We established causal relationships between three specific inflammatory factors and IDD. Elevated levels of MIP-1β [OR = 0.956, 95% CI: -0.08 to -0.006; P = 0.02] and IFN-G [OR = 0.915, 95% CI: -0.16 to -0.02; P = 0.01] expression were associated with a reduced risk of IDD. Conversely, genetic susceptibility to IDD was linked to a decrease in IL13 levels [OR = 0.967, 95% CI: -0.063 to -0.004; P = 0.03]. Conclusion In this study, we have identified inflammatory factors that exhibit a causal relationship with the onset and progression of IDD, as supported by genetic predictions.

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Causal relationships between circulating inflammatory factors and IgA vasculitis: a bidirectional Mendelian randomization study

Cited by 5 publications

References 74 publications

Genome-wide Mendelian Randomization analysis reveals specific inflammatory traits as causal risk factors for oral cancer

Genome-wide Mendelian Randomization analysis reveals specific inflammatory traits as causal risk factors for oral cancer

Deregulation in adult IgA vasculitis skin as the basis for the discovery of novel serum biomarkers

Causal Relationship Between Systemic Circulatory Inflammatory Regulators and Intervertebral Disc Degeneration: A Bidirectional Two-Sample Mendelian Randomization Study

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