Causal effects of gut microbiota on sepsis: a two-sample Mendelian randomization study

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Май 10, 2023

Background Recent studies had provided evidence that the gut microbiota is associated with sepsis. However, potential causal relationship remained unclear. Methods The present study aimed to explore effects between and sepsis by performing Mendelian randomization (MR) analysis utilizing publicly accessible genome-wide association (GWAS) summary-level data. Gut GWAS ( N = 18,340) were obtained from MiBioGen GWAS-summary-level data for gained UK Biobank (sepsis, 10,154 cases; 452,764 controls). Two strategies used select genetic variants, i.e., single nucleotide polymorphisms (SNPs) below locus-wide significance level (1 × 10 −5 ) statistical threshold (5 −8 chosen as instrumental variables (IVs). inverse variance weighted (IVW) was primary method MR study, supplemented a series of other methods. Additionally, set sensitivity methods, including MR-Egger intercept test, randomized polymorphism residual outlier (MR-PRESSO) Cochran’s Q leave-one-out carried out assess robustness our findings. Results Our suggested increased abundance Deltaproteobacteria, Desulfovibrionales, Catenibacterium , Hungatella negatively risk, while Clostridiaceae1, Alloprevotella, LachnospiraceaeND3007group Terrisporobacter positively correlated risk Sensitivity revealed no heterogeneity pleiotropy. Conclusion This firstly found suggestive beneficial or detrimental associations on applying approach, which may provide valuable insights into pathogenesis microbiota-mediated prevention treatment.

Язык: Английский

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Causal associations between modifiable risk factors and intervertebral disc degeneration

The Spine Journal, Год журнала: 2023, Номер 24(2), С. 195 - 209

Опубликована: Ноя. 6, 2023

Язык: Английский

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Multi-omic underpinnings of epigenetic aging and human longevity

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 19, 2023

Biological aging is accompanied by increasing morbidity, mortality, and healthcare costs; however, its molecular mechanisms are poorly understood. Here, we use multi-omic methods to integrate genomic, transcriptomic, metabolomic data identify biological associations with four measures of epigenetic age acceleration a human longevity phenotype comprising healthspan, lifespan, exceptional (multivariate longevity). Using transcriptomic imputation, fine-mapping, conditional analysis, 22 high confidence seven multivariate longevity. FLOT1, KPNA4, TMX2 novel, genes associated acceleration. In parallel, cis-instrument Mendelian randomization the druggable genome associates TPMT NHLRC1 aging, supporting imputation findings. Metabolomics identifies negative effect non-high-density lipoprotein cholesterol lipoproteins on longevity, but not Finally, cell-type enrichment analysis implicates immune cells precursors in and, more modestly, Follow-up cell traits suggests lymphocyte subpopulations lymphocytic surface molecules affect Our results highlight targets pathways involved facilitate comparisons clocks

Язык: Английский

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Causal relationship between immune cells and prostate cancer: a Mendelian randomization study

Frontiers in Cell and Developmental Biology, Год журнала: 2024, Номер 12

Опубликована: Март 19, 2024

Introduction: Despite the abundance of research indicating participation immune cells in prostate cancer development, establishing a definitive cause-and-effect relationship has proven to be difficult undertaking. Methods: This study employs Mendelian randomization (MR), leveraging genetic variables related from publicly available genome-wide association studies (GWAS), investigate this association. The primary analytical method used is inverse variance weighting (IVW) analysis. Comprehensive sensitivity analyses were conducted assess heterogeneity and horizontal pleiotropy results. Results: identifies four cell traits as causally contributing risk, including CD127- CD8+ T %CD8+ (OR = 1.0042, 95%CI:1.0011–1.0073, p 0.0077), CD45RA on CD39+ resting CD4 regulatory 1.0029, 95%CI:1.0008–1.0050, 0.0065), CD62L− Dendritic Cell Absolute Count 1.0016; 95%CI:1.0005–1.0026; 0.0039), CX3CR1 CD14+ CD16− monocyte 1.0024, 95%CI:1.0007–1.0040, 0.0060). Additionally, two are identified protective factors: 0.9975, 95%CI:0.9958–0.9992, 0.0047), FSC-A plasmacytoid 0.9983, 95%CI:0.9970–0.9995, 0.0070). Sensitivity indicated no pleiotropy. Discussion: Our MR provide evidence for causal between cancer, holding implications clinical diagnosis treatment.

Язык: Английский

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Genetics of migraine: complexity, implications, and potential clinical applications

The Lancet Neurology, Год журнала: 2024, Номер 23(4), С. 429 - 446

Опубликована: Март 18, 2024

Язык: Английский

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