Causal association of immune effector proteins with sepsis: A Mendelian randomization study DOI Creative Commons
Yongsheng Wang,

Chuchu Xu,

Yao Zhang

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(36), P. e39494 - e39494

Published: Sept. 6, 2024

Sepsis is an infection-induced systemic inflammatory response syndrome. Immune regulation plays a crucial role in sepsis. We looked into the link between immune effector–related proteins and sepsis this study by using both univariate multivariate Mendelian randomization (MR) analyses. accessed collected data from Integrative Epidemiology Unit’s Open About genome-wide association database. The 6 effector–associated each contained 10,534,735 single-nucleotide polymorphisms 3301 samples. Using weighted median, MR-Egger, simplex, inverse-variance weighting, mode methods, MR then investigated complement factor H-related protein-5 (CFHR5), Fc epsilon receptor II (FCER2), granzyme B (GZMB), major histocompatibility complex, class II, DQ alpha (HLA-DQA2), mannose-binding lectin 2 (MBL2), or myeloperoxidase (MPO) In results, P values of all were <0.05, suggesting possible causal relationship them MBL2 (odds ratio [OR] = 1.046) was risk for sepsis, while other (FCER2: OR 0.922; GZMB: 0.908; CFHR5: 0.858; HLA-DQA2: 0.896; MPO: 0.875) safety factors. By revealing CFHR5, FCER2, GZMB, HLA-DQA2, MBL2, MPO, our offers essential resource additional investigations on subject.

Language: Английский

Effects of circulating inflammatory proteins on spinal degenerative diseases: Evidence from genetic correlations and Mendelian randomization study DOI Creative Commons
Qingcong Zheng, Rongjie Lin, Du Wang

et al.

JOR Spine, Journal Year: 2024, Volume and Issue: 7(2)

Published: June 1, 2024

Abstract Background Numerous investigations have suggested links between circulating inflammatory proteins (CIPs) and spinal degenerative diseases (SDDs), but causality has not been proven. This study used Mendelian randomization (MR) to investigate the causal associations 91 CIPs cervical spondylosis (CS), prolapsed disc/slipped disc (PD/SD), canal stenosis (SCS), spondylolisthesis/spondylolysis. Methods Genetic variants data for SDDs were obtained from genome‐wide association studies (GWAS) database. We inverse variance weighted (IVW) as primary method, analyzing validity robustness of results through pleiotropy heterogeneity tests performing reverse MR analysis test causality. Results The IVW with Bonferroni correction indicated that beta‐nerve growth factor (β‐NGF), C‐X‐C motif chemokine 6 (CXCL6), interleukin‐6 (IL‐6) can increase risk CS. Fibroblast 19 (FGF19), sulfotransferase 1A1 (SULT1A1), tumor necrosis factor‐beta (TNF‐β) PD/SD risk, whereas urokinase‐type plasminogen activator (u‐PA) decrease PD/SD. FGF19 TNF SCS risk. STAM binding protein (STAMBP) T‐cell surface glycoprotein CD6 isoform (CD6 isoform) spondylolisthesis/spondylolysis, monocyte chemoattractant 2 (MCP2) latency‐associated peptide transforming beta 1 (LAP‐TGF‐β1) spondylolisthesis/spondylolysis Conclusions multiple genetically predicted four (CS, PD/SD, SCS, spondylolisthesis/spondylolysis). provides reliable genetic evidence in‐depth exploration involvement in pathogenic mechanism novel potential targets SDDs.

Language: Английский

Citations

7
Enhancing insight into ferroptosis mechanisms in sepsis: A genomic and pharmacological approach integrating single-cell sequencing and Mendelian randomization DOI

Yuanqi Zhao,

Zijian Zhou,

Xiuyu Cui

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 140, P. 112910 - 112910

Published: Aug. 8, 2024

Language: Английский

Citations

1
Unraveling the causal associations between systemic cytokines and six inflammatory skin diseases DOI

Waner Liu,

Xu Zhang, Xiang Chen

et al.

Cytokine, Journal Year: 2024, Volume and Issue: 185, P. 156810 - 156810

Published: Dec. 3, 2024

Language: Английский

Citations

1
No Genetic Causality between Branched-Chain Amino Acids and Diabetic Nephropathy: A Two-Sample Mendelian Randomization Study DOI Creative Commons
Qiqi Ma,

Shuaihua Song,

Gaosi Xu

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 25, 2024

Abstract Background Numerous studies have reported the close relationship between branched-chain amino acids (BCAA) and diabetic nephropathy (DN). Nevertheless, whether there is a genetically causal association them remains profoundly elusive. Methods A two-sample Mendelian randomization (MR) analysis was performed using large genome-wide of European population. The primarily evaluated by inverse variance weighted (IVW) method. In addition, MR-Egger regression, median, simple mode, MR-weighted mode were also conducted as supplemented methods. For sensitivity, Cochrane’s Q test, MR-PRESSO employed to evaluate heterogeneity pleiotropy, respectively. Results According IVW method, no significant effect measured three BCAA DN (valine: OR: 1.202, 95% CI: 0.714–2.023, P = 0.488; isoleucine: 0.878, 0.400–1.924, 0.744; leucine: 1.395, 0.686–2.839, 0.358; total BCAA: 1.374, 0.703–2.685, 0.352). reverse MR analysis, an exposure factor had on 1.004, 0.994–1.014, 0.412; 0.999, 0.990–1.009, 0.910; 1.001, 0.992–1.011, 0.802; 1.002, 0.993–1.012, 0.628). Conclusion Our results first demonstrated at genetic level.

Language: Английский

Citations

0
Causal association of circulating cytokines with the risk of lung cancer: a Mendelian randomization study DOI Creative Commons

Dachen Luo,

Zonglian Gong,

Qingyuan Zhan

et al.

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

Published: June 18, 2024

Background Lung cancer is the deadliest and most prevalent malignancy worldwide. While smoking an established cause, evidence to identify other causal factors remains lacking. Current research indicates chronic inflammation involved in tumorigenesis development, though specific mechanisms underlying role of inflammatory cytokines lung pathogenesis remain unclear. This study implemented Mendelian randomization (MR) analysis investigate effects circulating on development. Methods We performed a two-sample MR Europeans utilizing publicly available genome-wide association summary statistics. Single nucleotide polymorphisms significantly associated with cytokine were selected as genetic instrumental variables. Results Genetically predicted levels chemokine interleukin-18 (IL-18) (OR = 0.942, 95% CI: 0.897–0.990, P 0.018) exerted significant negative overall risk this analysis. Examining histologic subtypes revealed further associations. Stem cell factor (SCF) 1.150, 1.021–1.296, 0.021) interleukin-1beta (IL-1β) 1.152, 1.003–1.325, 0.046) positively adenocarcinoma risk, no showed links squamous risk. Stratified by status, interferon gamma-induced protein 10 (IP-10) 0.861, 0.781–0.950, 0.003) was inversely while IL-1β 1.190, 1.023–1.384, 0.024) ever smokers. Among never smokers, positive observed between SCF 1.474, 1.105–1.964, 0.008). Importantly, these inferences remained robust across multiple complementary approaches, including MR-Egger, weighted median, mode simple regressions. Sensitivity analyses also excluded potential bias stemming from pleiotropy. Conclusion found preliminary that genetically four cytokines—SCF, IL-1β, IL-18, IP-10—may causally influence subtype-specific manner, well stratified status. Identifying pathways may promote carcinogenesis represents new targets for prevention, early detection, treatment deadly malignancy.

Language: Английский

Citations

0
Avaliação dos critérios clínicos e utilização de biomarcadores na triagem da sepse fora da unidade de terapia intensiva DOI Creative Commons

Francine Sanchez Gulin

Published: March 25, 2024

A sepse, principal causa de morte por infecções,

Citations

0
Sjögren’s syndrome and Parkinson’s disease: a bidirectional Mendelian randomization study DOI Creative Commons

Xi Yin,

Miao Wang,

Fengzhu Li

et al.

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

Published: July 22, 2024

Previous epidemiological studies have reported an association between Sjögren's syndrome (SS) and Parkinson's disease (PD); however, the causality direction of this relationship remain unclear. In study, we aimed to investigate causal genetically determined SS risk PD using bidirectional Mendelian randomization (MR).

Language: Английский

Citations

0
Causal association of immune effector proteins with sepsis: A Mendelian randomization study DOI Creative Commons
Yongsheng Wang,

Chuchu Xu,

Yao Zhang

et al.

Medicine, Journal Year: 2024, Volume and Issue: 103(36), P. e39494 - e39494

Published: Sept. 6, 2024

Sepsis is an infection-induced systemic inflammatory response syndrome. Immune regulation plays a crucial role in sepsis. We looked into the link between immune effector–related proteins and sepsis this study by using both univariate multivariate Mendelian randomization (MR) analyses. accessed collected data from Integrative Epidemiology Unit’s Open About genome-wide association database. The 6 effector–associated each contained 10,534,735 single-nucleotide polymorphisms 3301 samples. Using weighted median, MR-Egger, simplex, inverse-variance weighting, mode methods, MR then investigated complement factor H-related protein-5 (CFHR5), Fc epsilon receptor II (FCER2), granzyme B (GZMB), major histocompatibility complex, class II, DQ alpha (HLA-DQA2), mannose-binding lectin 2 (MBL2), or myeloperoxidase (MPO) In results, P values of all were <0.05, suggesting possible causal relationship them MBL2 (odds ratio [OR] = 1.046) was risk for sepsis, while other (FCER2: OR 0.922; GZMB: 0.908; CFHR5: 0.858; HLA-DQA2: 0.896; MPO: 0.875) safety factors. By revealing CFHR5, FCER2, GZMB, HLA-DQA2, MBL2, MPO, our offers essential resource additional investigations on subject.

Language: Английский

Citations

0