The causal relationship between thoracic aortic aneurysm and immune cells: a mendelian randomization study
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ABSTRACT:
SUBMITTER: Liu G
PROVIDER: S-EPMC11020992 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Thoracic aortic aneurysm (TAA) is associated with changes in the levels of metabolites; however, the exact causal relationships remain unclear. Identifying this complex relationship may provide new insights into the pathogenesis of TAA. We used genome-wide association studies to investigate the relationship between metabolites and TAA in this study. A total of 1400 serum metabolites were investigated for their potential causal effects on the risk of TAA. We performed bidirectional and 2-sample Mendelian randomization (MR) analysis using 5 MR tests: MR-Egger, weighted mode, weighted median, inverse variance weighted (IVW), and simple mode. We also performed sensitivity analysis to verify our findings, including heterogeneity analysis using IVW and MR-Egger tests and pleiotropy analysis using the MR-Egger test. Multiple metabolites were identified as having a causal effect on the risk of TAA, particularly those related to lipid metabolites; the top 2 risk factors identified using the IVW test were 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (P = .019) and 5alpha-androstan-3alpha,17alpha-diol (P = .021), whereas the 2 top protective factors were 1-stearoyl-2-docosahexaenoyl-gpc (P = .023) and 1-oleoyl-2-docosahexaenoyl-GPC (P = .005). Sensitivity analysis verified the lack of heterogeneity (P = .499, .584, .232, and .624, respectively; IVW test) or pleiotropy (P = .621, .483, .598, and .916, respectively; Egger test). Our study provides new evidence of a causal relationship between metabolites and the risk of TAA, thus providing new insights into the pathogenesis of this disease. These findings suggest a promising approach for metabolite-based therapeutic interventions.
| S-EPMC11404878 | biostudies-literature
Project description:MethodsWe sourced genetic association data from public genome-wide association study databases for populations of European ancestry. Adhering to MR principles, we identified valid instrumental variables from genetic variants. A range of statistical methods were applied for MR analysis, with the inverse variance weighted (IVW) method emerging as the most reliable estimator of causality in this context.ResultsThe causal estimates obtained using the IVW method revealed a significant association between genetically predicted AA and rheumatoid arthritis (RA; OR = 1.06, 95% CI = 1.01-1.12, P=0.029). Conversely, genetically predicted RA showed nonsignificant causal estimates of AA (OR = 0.97, 95% CI = 0.92-1.02, P=0.204). Additionally, there was no evidence to suggest that AA may increase the risk of inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), systemic lupus erythematosus (SLE), and psoriasis (PSO). The sensitivity analysis confirmed the absence of heterogeneity or horizontal pleiotropy effects.ConclusionOur findings shed light on the causal effects between genetically predisposed AA and RA. They also suggest the potential clinical utility of human leukocyte antigen (HLA) risk genetic markers for developing personalized treatment and prevention strategies.
| S-EPMC11483648 | biostudies-literature
Project description: Not available
| S-BSST1516 | biostudies-other
Project description:This study employed Mendelian randomization (MR) analysis to explore potential causal relationships between 731 immune cell subtypes and periodontitis. Utilizing a 2-sample MR design, our study delved into the diverse landscape of immune cell interactions with periodontitis-associated factors. Multiple MR methods, including inverse variance weighting, weighted median, and MR-Egger tests, were employed to ensure reliability and mitigate potential pleiotropic effects. The study revealed significant causal effects (FDR < 0.15) between immune cells (B cells, maturation stages of T cells, Treg) and periodontitis. Notably, receptors like triggering receptor expressed on myeloid cells-1 (TREM-1) and triggering receptor expressed on myeloid cells-2 (TREM-2) exhibited intricate roles, warranting further investigation. In conclusion, this MR analysis elucidates complex causal relationships between immune cell subtypes and periodontitis. The findings provide a foundation for understanding systemic implications, offering insights for clinical practice and highlighting avenues for future research.
| S-EPMC11651513 | biostudies-literature
Project description:BackgroundThe causal relationship between immune cells and telomere length remains controversial.MethodsData on the immune cells were obtained from a previous study with 3,757 participants. Data on telomere length were obtained from the OpenGWAS database. Genome-Wide Association Study (GWAS) data were obtained and screened for eligible instrumental variables (IVs) using the TwoSampleMR package and the Phenoscanner database. To investigate the genetic causality between immune cells and telomere length, Mendelian randomization (MR) analysis and Bayesian weighted Mendelian randomization (BWMR) analysis were used.ResultsMR analysis showed that there is indeed a genetic causal relationship between immune cells and telomere length. A total of 16 immune cells were successfully validated. A positive correlation was found between telomere length and immune cells such as CD28 + CD45RA + CD8br %CD8br (OR = 1.002, 95%CI: 1.000-1.003). A negative correlation was found between telomere length and immune cells such as Transitional AC (OR = 0.991, 95%CI: 0.984-0.997) (P < 0.05). Reverse MR analysis similarly confirmed that telomere length can affect four types of immune cells, including CD25 on IgD + CD24- (OR = 1.291, 95%CI: 1.060-1.571), at the genetic level.ConclusionThere is indeed a mutual genetic causality between immune cells and telomere length, which will provide theoretical basis and support for more subsequent clinical studies.
| S-EPMC10924351 | biostudies-literature
Project description:Background: Cerebral aneurysms (CAs) are a significant cerebrovascular ailment with a multifaceted etiology influenced by various factors including heredity and environment. This study aimed to explore the possible link between different types of immune cells and the occurrence of CAs. Methods: We analyzed the connection between 731 immune cell signatures and the risk of CAs by using publicly available genetic data. The analysis included four immune features, specifically median brightness levels (MBL), proportionate cell (PC), definite cell (DC), and morphological attributes (MA). Mendelian randomization (MR) analysis was conducted using the instrumental variables (IVs) derived from the genetic variation linked to CAs. Results: After multiple test adjustment based on the FDR method, the inverse variance weighted (IVW) method revealed that 3 immune cell phenotypes were linked to the risk of CAs. These included CD45 on HLA DR+NK (odds ratio (OR), 1.116; 95% confidence interval (CI), 1.001-1.244; p = 0.0489), CX3CR1 on CD14- CD16- (OR, 0.973; 95% CI, 0.948-0.999; p = 0.0447). An immune cell phenotype CD16- CD56 on NK was found to have a significant association with the risk of CAs in reverse MR study (OR, 0.950; 95% CI, 0.911-0.990; p = 0.0156). Conclusion: Our investigation has yielded findings that support a substantial genetic link between immune cells and CAs, thereby suggesting possible implications for future clinical interventions.
| S-EPMC10834707 | biostudies-literature
Project description:BackgroundObservational studies have reported an inverse association of type 2 diabetes (T2D) with thoracic aortic aneurysm (TAA). However, the causality of the association has not been established yet. The present study aims to clarify the causal relationship between T2D and TAA via a Mendelian randomization (MR) approach.MethodsCausality of associations were assessed using a two-sample MR framework. Genome-wide association study (GWAS) summary statistics were obtained for T2D, glycated hemoglobin (HbA1c), fasting glucose (FG) and fasting insulin (FI) as exposures, and TAA, ascending aortic diameter (AAoD) and descending aortic diameter (DAoD) as outcomes. Four different methods (inverse variance weighted [IVW], weight median, MR-Egger and MR-PRESSO) were used to calculate causal estimates. Heterogeneity and horizontal pleiotropy were assessed using Cochran Q test and MR-Egger regression intercept, respectively.ResultsGenetically predicted T2D was inversely associated with the risk of TAA (OR: 0.931, 95% CI 0.870 to 0.997, p = 0.040, IVW method) and AAoD (Beta: -0.065, 95%CI -0.099 to - 0.031, p = 1.7e-04, IVW method), but not with DAoD (p > 0.05). Genetically predicted FG level was inversely associated with AAoD (Beta: -0.273, 95% CI -0.396 to -0.150, p = 1.41e-05, IVW method) and DAoD (Beta: -0.166, 95% CI -0.281 to -0.051, p = 0.005, IVW method), but not with TAA (p > 0.05). The effect of genetically predicted HbA1c and FI on TAA, AAoD and DAoD did not reach statistical significance (p > 0.05).ConclusionsGenetic predisposition to T2D decreases the risk of TAA. Genetically predicted T2D is inversely associated with AAoD, but not with DAoD. Genetically predicted FG level was inversely associated with AAoD and DAoD.
| S-EPMC10245418 | biostudies-literature
Project description:IntroductionDespite the abundance of research indicating the participation of immune cells in prostate cancer development, establishing a definitive cause-and-effect relationship has proven to be a difficult undertaking.MethodsThis study employs Mendelian randomization (MR), leveraging genetic variables related to immune cells from publicly available genome-wide association studies (GWAS), to investigate this association. The primary analytical method used in this study is inverse variance weighting (IVW) analysis. Comprehensive sensitivity analyses were conducted to assess the heterogeneity and horizontal pleiotropy of the results.ResultsThe study identifies four immune cell traits as causally contributing to prostate cancer risk, including CD127- CD8+ T cell %CD8+ T cell (OR = 1.0042, 95%CI:1.0011-1.0073, p = 0.0077), CD45RA on CD39+ resting CD4 regulatory T cell (OR = 1.0029, 95%CI:1.0008-1.0050, p = 0.0065), CD62L- Dendritic Cell Absolute Count (OR = 1.0016; 95%CI:1.0005-1.0026; p = 0.0039), CX3CR1 on CD14+ CD16- monocyte (OR = 1.0024, 95%CI:1.0007-1.0040, p = 0.0060). Additionally, two immune cell traits are identified as causally protective factors: CD4 on monocyte (OR = 0.9975, 95%CI:0.9958-0.9992, p = 0.0047), FSC-A on plasmacytoid Dendritic Cell (OR = 0.9983, 95%CI:0.9970-0.9995, p = 0.0070). Sensitivity analyses indicated no horizontal pleiotropy.DiscussionOur MR study provide evidence for a causal relationship between immune cells and prostate cancer, holding implications for clinical diagnosis and treatment.
| S-EPMC10985200 | biostudies-literature
Project description:Immunity and inflammation in pulmonary arterial hypertension (PAH) has gained more attention. This research aimed to investigate the potential causal connections between 731 immunophenotypes and the likelihood of developing PAH. We obtained immunocyte data and PAH from openly accessible database and used Mendelian randomization (MR) analysis to evaluate the causal association between each immunophenotype and PAH. Various statistical methods were employed: the MR-Egger, weighted median, inverse variance weighted (IVW), simple mode, and weighted mode. In the study of 731 different types of immune cells, it was found that 9 showed a potential positive connection (IVW P < .05) with increased risk of PAH, while 19 had a possible negative link to decreased risk. Following false discovery rate (FDR) adjustment, the analysis using the IVW method demonstrated that 5 immune phenotypes were significantly associated with PAH (FDR < 0.05, OR > 1). Conversely, there was a negative correlation between PAH and 4 immune cell types (FDR < 0.05, OR < 1). Sensitivity analyses suggested the robustness of all MR findings. This research, for the first time, has revealed indicative evidence of a causal link between circulating immune cell phenotypes and PAH through genetic mechanisms. These results underscore the importance of immune cells in the pathogenesis of PAH.
| S-EPMC11404942 | biostudies-literature
Project description:PurposeThis article explored the causal relationship between immune cells and diabetic retinopathy (DR) using single nucleotide polymorphisms (SNPs) as an instrumental variable and Mendelian randomization (MR).MethodsStatistical data were collected from a publicly available genome-wide association study (GWAS), and SNPs that were significantly associated with immune cells were used as instrumental variables (IVs). Inverse variance weighted (IVW) and MR-Egger regression were used for MR analysis. A sensitivity analysis was used to test the heterogeneity, horizontal pleiotropy, and stability of the results.ResultsWe investigated the causal relationship between 731 immune cells and DR risk. All the GWAS data were obtained from European populations and from men and women. The IVW analysis revealed that HLA DR on CD14+ CD16- monocytes, HLA DR on CD14+ monocytes, HLA DR on CD33-HLA DR+, HLA DR on CD33+ HLA DR+ CD14- on CD33+ HLA DR+ CD14dim, and HLA DR on myeloid dendritic cells may increase the risk of DR (P<0.05). HLA DR to CD14-CD16- cells, the monocytic myeloid-derived suppressor cell absolute count, the SSC-A count of CD4+ T cells, and terminally differentiated CD4+ T cells may be protective factors against DR (P<0.05). The sensitivity analysis indicated no heterogeneity or pleiotropy among the selected SNPs. Furthermore, gene annotation of the SNPs revealed significant associations with 10 genes related to the risk of developing PDR and potential connections with 12 other genes related to PDR.ConclusionMonocytes and T cells may serve as new biomarkers or therapeutic targets, leading to the development of new treatment options for managing DR.
| S-EPMC11406504 | biostudies-literature