Osteomyelitis and immune cell phenotypes: a study based on a Mendelian randomisation approach DOI Creative Commons

Kehan Long,

Sumiao Dong,

Dou Yu

et al.

Research Square (Research Square), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 26, 2023

Abstract Background: Osteomyelitis is a severe bone marrow infection, whose pathogenesis not fully understood. This study aims to explore the causal relationship between immune cell characteristics and osteomyelitis, in hopes of providing new insights for prevention treatment osteomyelitis. Methods: Based on two independent samples, this employed two-sample Mendelian randomization (MR) analysis assess 731 (divided into 7 groups) Genetic variants were used as proxies risk factors ensure selected instrumental variables meet three key assumptions MR analysis. GWAS data came from public catalog, while osteomyelitis was sourced Finnish database. Results: At significance level 0.05, 21 phenotypes identified having with development In B group, such Memory %B cell, CD20- %lymphocyte showed positive Naive-mature IgD- CD38- AC negative relationship. addition, specific cDC Myeloid TBNK T maturation stage, Treg group also significant associations Through reverse analysis, it found that had no impact these phenotypes, suggesting occurrence might turn affect phenotypes. Conclusion: reveals first time perspective understanding mechanism These findings are formulating targeted strategies, hold promise improving clinical outcomes patients’

Language: Английский

Mendelian randomization studies of risk and protective factors for osteoporosis: a systematic review and meta-analysis DOI Creative Commons

Wenhao Ji,

Bin Pan, Xin Chen

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 16, 2025

Mendelian randomization is believed to attenuate the biases inherent in observational studies, yet a meta-analysis of studies osteoporosis has not been conducted thus far. This study aims evaluate connection between potential causal factors and risk by synthesizing evidence from studies. The databases PubMed, Web Science, Embase were systematically searched for investigating influencing up May 2024. Meta-analyses assess associations various pathogenic using Randomization quality was evaluated according Strengthening Reporting Observational Studies Epidemiology via (STROBE-MR) guidelines. A total 706 potentially relevant articles screened, resulting inclusion 53 systematic review, which 30 eligible meta-analysis. combined findings these revealed that rheumatoid arthritis, inflammatory bowel disease, sex hormone binding globulin, depression, non-alcoholic fatty liver primary biliary cholangitis asthma are associated with increased osteoporosis, while basal metabolic rate gut microbiota (NB1n) serves as protective factor. However, association obesity, type 2 diabetes mellitus, metformin, ulcerative colitis, leisure sedentary behaviors, systemic lupus erythematosus, serum iron found be nonsignificant. In summary, our indicates significant relationships osteoporosis's onset progression have established cholangitis, rate, (NB1n), asthma. https://www.crd.york.ac.uk/prospero/, identifier PROSPERO CRD42024540504.

Language: Английский

Citations

1

Genus_Ruminococcus and order_Burkholderiales affect osteoporosis by regulating the microbiota-gut-bone axis DOI Creative Commons
Ning Li, Haiyang Wang,

Huan Pei

et al.

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

Published: May 21, 2024

Background This study aimed to clarify the relationship between gut microbiota and osteoporosis combining Mendelian randomization (MR) analysis with animal experiments. Methods We conducted an on differential bacteria using open-access genome-wide association (GWAS) data microbe obtained from public databases. The was performed two-sample MR analysis, causal examined through inverse variance weighting (IVW), Egger, weighted median, mode methods. Bilateral oophorectomy employed replicate mouse model, which assessed by micro computed tomography (CT), pathological tests, bone transformation indexes. Additionally, 16S rDNA sequencing fecal samples, while SIgA indexes of IL-6, IL-1β, TNF-α inflammatory factors were in colon samples. Through immunofluorescence histopathology, expression levels tight junction proteins, such as claudin-1, ZO-1, occludin, assessed, conduct correlation related environmental performed. Results A positive observed g_Ruminococcus1 risk osteoporosis, O_Burkholderiales showed a negative osteoporosis. Furthermore, there no evidence heterogeneity or pleiotropy. successful replication model it found that abundance significantly reduced, g_Ruminococcus increased ovariectomized (OVX)-mice. intestinal level OVX mice decreased, increased, barrier damage occurred, content LPS serum increased. is strongly positively correlated formation factors, indicators, density, volume fraction, trabecular quantity, whereas negatively resorption shows strong factors. Conclusion may regulate development microbiota-gut-bone axis.

Language: Английский

Citations

6

Exploring the immunological landscape of osteomyelitis through mendelian randomization analysis DOI Creative Commons

Kehan Long,

Ao Gong, Dou Yu

et al.

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

Published: April 8, 2024

Osteomyelitis is a severe bone marrow infection, whose pathogenesis not yet fully understood. This study aims to explore the causal relationship between immune cell characteristics and osteomyelitis, hoping provide new insights for prevention treatment of osteomyelitis. Based on two independent samples, this employed two-sample Mendelian randomization (MR) analysis assess 731 (divided into seven groups) Genetic variants were used as proxies risk factors ensure that selected instrumental variables meet three key assumptions MR analysis. Genome-Wide Association Studies (GWAS) data obtained from public GWAS catalog, while osteomyelitis was sourced FinnGen. At significance level 0.05, 21 phenotypes identified having with development. In B group, such Memory % (percentage memory cells within total population, finger ratio), CD20- %B do express CD20 marker their surface), lymphocyte showed positive Naive-mature IgD-CD38-absolute counts (AC) negative relationship. addition, specific in conventional dendritic (cDCs) Myeloid TBNK (T cells, natural killer cells) T maturation stage, Treg group also significant associations Through reverse analysis, it found had no impact these phenotypes, suggesting occurrence may affect phenotypes. To our knowledge, first shed light development thereby providing perspective understand mechanism These findings are formulating targeted strategies, hold promise improve outcomes patients

Language: Английский

Citations

3

Thyroid cancer and cardiovascular diseases: a Mendelian randomization study DOI Creative Commons
Yamei Gao, Zhijia Wang, Jinsheng Yu

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2024, Volume and Issue: 11

Published: April 25, 2024

Background Multiple observational studies have shown associations between thyroid cancer (TC) and cardiovascular diseases (CVDs). However, the results were inconsistent, potential causal genetic relationship remains unclear. Methods The instruments of TC CVDs derived from data obtained through genome-wide association (GWAS). We performed two-sample Mendelian randomization(MR) methods to investigate causality on CVDs. Summary-level statistics for CVDs, including heart failure (HF), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), ischemic stroke (IS) venous thromboembolism (VTE). primary method employed in this MR analysis was Inverse Variance Weighted (IVW) approach, four additional algorithms used: MR-Egger, weighted median, simple mode, mode. Additionally, we assessed reliability pleiotropy, heterogeneity leave-one-out sensitivity analysis. Results In analysis, only detected genetically predicted HF (IVW method, odds ratio (OR) = 1.00134, 95% confidence interval (CI): 1.00023–1.00244, p 0.017). There no with CAD, MI, AF, IS, VTE. Conclusion Our confirmed HF. It is crucial closely monitor incidence patients give comprehensive clinical intervention based conventional treatment.

Language: Английский

Citations

3

Breast Cancer and Meningioma Risk: A Mendelian Randomization Study DOI Creative Commons
Jian‐Wei Huang, Yifei Wang, Yongxian Hu

et al.

Brain and Behavior, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

ABSTRACT Background The exact nature of the link between breast cancer and meningiomas is unknown, although observational studies have shown a correlation two. Using two‐sample Mendelian randomization (MR) strategy, we aimed to investigate effect on meningiomas. Methods Three sets genetic instruments were utilized in this study based publicly available summary data. For cancer, selected 62 strongly associated SNPs; separate datasets curated for HER2‐positive HER2‐negative subtypes. MR analyses included outlier testing, MR‐Egger regression, MR‐PRESSO, weighted median, inverse variance approaches. Results analysis demonstrated significant evidence cancer's meningioma risk (OR = 1.213, 95% CI 1.054–1.396, p 0.007), supported by 1.456, 1.066–1.988, 0.021) though not median method 1.095, 0.914–1.311, 0.326). Inverse weighting specifically revealed association incidence 1.203, 1.048–1.381, 0.009). Furthermore, was with an increased malignant 1.64, 1.12–2.40, 0.011). Conclusions This represents first investigating causal relationship Our findings support hypothesis that may increase risk.

Language: Английский

Citations

0

Identification of key genes and diagnostic biomarkers for peripheral atherosclerosis: A multi-omics approach DOI Creative Commons
Lixue Huang, Han Li, Qing Lin

et al.

Medicine, Journal Year: 2025, Volume and Issue: 104(21), P. e42437 - e42437

Published: May 23, 2025

Peripheral atherosclerosis (PAS), characterized by lipid plaque accumulation in arterial walls, significantly increases cardiovascular risk. This study aimed to identify molecular biomarkers and elucidate underlying mechanisms of PAS progression. We analyzed 2 gene expression omnibus datasets (GSE28829, GSE100927) differentially expressed genes ( P < .05, |log FC| ≥ 0.585). Functional enrichment (Gene Ontology/Kyoto Encyclopedia Genes Genomes) Mendelian randomization analyses were performed using genome-wide association quantitative trait loci data. Six hub validated through single-cell RNA sequencing independent datasets. A diagnostic nomogram was developed evaluated calibration curves, decision curve analysis, receiver operating characteristic metrics. Integrated analysis revealed 6 key PAS-associated (leukocyte immunoglobulin-like receptor B1, hematopoietic cell-specific lyn substrate 1, plasminogen activator urokinase, C-type lectin domain family member B, phosphatidylinositol-4-phosphate 5-kinase type 1 beta, cofilin 2). The model demonstrated exceptional accuracy, achieving area under the curves 1.0 (training) 0.975 (validation). confirmed causal relationships, with beta showing protective effects (odds ratio 0.74–0.90), while leukocyte urokinase emerged as risk factors. multi-omics identifies novel signatures establishes a robust tool. findings advance our understanding pathogenesis pave way for personalized therapeutic strategies.

Language: Английский

Citations

0

Genetic support of the causal association between gut microbiota and peripheral artery disease: a bidirectional Mendelian randomization study DOI Creative Commons
Hongshuo Shi, Xin Yuan, Fangfang Wu

et al.

Aging, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 9, 2024

Background: The causal relationship between gut microbiota and peripheral artery disease (PAD) is still not clear. In this research, we employed the Mendelian randomization (MR) technique to explore potential connection 211 species PAD. We also investigated whether effects operate in both directions. Methods: used Genome-wide Association Studies (GWAS) summary statistics data from MiBioGen FinnGen consortia conduct a two-sample MR analysis link Sensitivity conducted assess robustness of results. addition that, reverse was performed examine inverse relationship. Results: variance weighted (IVW) method provided evidence supporting 9 specific taxa study findings indicated that family Family XI (OR=1.11, CI 1.00-1.24, P=0.048), genus Lachnoclostridium (OR=1.24, 1.02-1.50, P=0.033), Lachnospiraceae UCG001 (OR=1.17, 1.01-1.35, P=0.031) are risk factors associated with class Actinobacteria (OR=0.84, 0.72-0.99, P=0.034), Acidaminococcaceae (OR=0.80, 0.66-0.98, P=0.029), Coprococcus2 (OR=0.79, 0.64-0.98, Ruminococcaceae UCG004 P=0.032), UCG010 (OR=0.74, 0.58-0.96, P=0.022), order NB1n (OR=0.88, 0.79-0.98, P=0.02) may be Moreover, our did uncover any PAD nine investigated. Conclusions: Our research has confirmed while identifying bacterial communities

Language: Английский

Citations

2

Exploring causal correlations between inflammatory cytokines and colorectal cancer: A 2-sample Mendelian randomization study DOI Creative Commons
Heran Zhou, Xuefei Yang,

Qujia Yang

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(44), P. e40230 - e40230

Published: Nov. 1, 2024

Colorectal cancer (CRC) is a significant global public health concern. Several observational studies have examined the association between inflammatory cytokines and risk of colorectal cancer, but findings been inconsistent. In this study, we employed 2-sample Mendelian randomization (MR) analysis, primarily using inverse variance weighted approach, to investigate causal relationship CRC. The forward MR analysis revealed positive higher levels interleukin (IL)-16 (OR: 1.37, P = .002), vascular endothelial growth factor 1.44, .001), MIG 1.23, .040) with an increased rectal cancer. Conversely, macrophage colony-stimulating 0.80, .010) may potentially decrease colon reverse it was found that linked IL-1b 0.93, .022), IL-1ra 0.90, IL-5 IL-9 .017), TNF-a 0.91, .003). Additionally, associated elevated FGF-Basic 1.10, .028). Consistent results were also in MR-Egger, median, mode analysis. Our study presents novel evidence supporting

Language: Английский

Citations

1

Causal association between psoriasis vulgaris and bullous pemphigoid: a two-sample bidirectional Mendelian randomization study DOI Creative Commons

Aobei Zhang,

Zhihui Yang, Tao Huang

et al.

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

Published: March 13, 2024

The association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown. To investigate whether there is a causal effect BP. Two-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide studies (GWAS) summary statistics. GWAS statistics for BP downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 cases 218,066 controls. data extracted Sakaue et al., comprises 5072 478,102 Single-nucleotide polymorphisms (SNPs) associated with exposure selected as instrumental variables by performing additional quality control steps. inverse-variance-weighted (IVW) method was used primary MR analyses, MR-Egger regression, weighted mode method, median simple employed sensitivity analyses. intercept test "leave-one-out" analysis performed to evaluate horizontal pleiotropy potentially influential SNPs, respectively. Genetically determined log odds an increased risk (IVW: ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, P=0.038). Sensitivity (OR=1.255, 95%CI: 0.973-1.618, P=0.106), Egger (OR=1.315, 0.951-1.817, P=0.126), (OR=1.414, 0.823-2.429, P=0.234) (OR=1.177, 0.889-1.559, P=0.254) derived directionally consistent relationship genetically predicted risks developing On contrary, we found that had no significant on OR=0.996, P= 0.707), indicating unidirectionality relationship. tests showed evidence pleiotropy. No SNP driving results detected leave-one-out analysis. Our suggested causally increases BP, highlighting need potential strategies prevention early diagnosis comorbid in patients vulgaris. Further researches into this underlying mechanisms are warranted.

Language: Английский

Citations

1

The causal relationship between psoriasis and cancers: a two-sample Mendelian randomization analysis DOI Creative Commons

Jiaye Long,

Miyang Yang,

Yingrong Pang

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: March 21, 2024

Background Although observational studies suggest a correlation between psoriasis (PS) and cancers, it is still unknown whether this association can replace causal relationships due to the limitations of studies. Therefore, we conducted two-sample Mendelian randomization (MR) analysis evaluate relationship PS cancers. Methods genetic summary data were obtained from two genome-wide (GWAS). We employed MR Base for individuals retrieving tumors distinct locations. Inverse-variance weighted was principal method used MR, supplemented by median, Egger, simple mode, mode. To investigate possible link performed independent meta-analysis based on analyses. Results Two analyses both found no significant overall cancers (OR=1.0000, 95% confidence interval [CI]:0.9999-1.0001, P =0.984; OR=1.0000, CI:0.9999-1.0001, =0.761), with 17 site-specific In analyses, there CI: 0.9999-1.0001, =1.00, I 2 = 0.0%), Conclusions Our findings do not support More population-based experimental investigations will be required better understand complicated

Language: Английский

Citations

0