Causal Evaluation of Laboratory Markers in Type 2 Diabetes on Cancer and Vascular Diseases Using Various Mendelian Randomization Tools

Jin, Heejin; Lee, Sanghun; Won, Sungho

doi:10.3389/fgene.2020.597420

Cited by 23 publications

(33 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Assumption checks for determining the main analytic tools were done for all 41 regulators. Except for monocyte-specific chemokine 3 (MCP3), monokine induced by interferon gamma (MIG), and TNF-related apoptosis-inducing ligand (TRAIL), all cytokines were analyzed using the IVW methodology as the primary analytical method, with no evidence of heterogeneity and no week instruments ( 21 ). For MCP3, MR-Egger (SIMEX) was chosen as the primary approach because the p -values for the Q -tests from IVW and MR-Egger were both below 0.05, and I 2 was lower than 90%.…”

Section: Resultsmentioning

confidence: 99%

“…The heterogeneity for three cytokines became insignificant once the outliers were removed ( I 2 : 15.1%; Cochrane’s Q p = 0.21; I 2 : 12.8%; Cochrane’s Q p = 0.25; I 2 : 0%; Cochrane’s Q p = 0.48), so IVW was also applicable as the main test. For MCP1, MR-Egger (SIMEX) was implemented as the concluding results with heterogeneity existence, I 2 <90% and InSIDE assumption fulfillment ( 21 ) ( Supplementary Table S5 ).…”

Section: Resultsmentioning

confidence: 99%

“…The major assessment for each regulator among all these approaches listed above was chosen in accordance with the recommended strategy, which would take into account three fundamental assumptions, NOME and InSIDE. ( 21 ). If MR-PRESSO reports any outlier SNPs, the outliers will be first excluded, and the remaining IVs will then be further assessed for the suitable statistical strategy.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization

et al. 2023

View full text Add to dashboard Cite

ObjectivesPrevious studies have reported that a few inflammatory cytokines have associations with systemic lupus erythematosus (SLE)—for example, IL-6, IL-17, and macrophage inflammatory protein (MIP). This Mendelian randomization was conducted to further assess the causal correlations between 41 inflammatory cytokines and SLE.MethodsThe two-sample Mendelian randomization utilized genetic variances of SLE from a large publicly available genome-wide association study (GWAS) (7,219 cases and 15,991 controls of European ancestry) and inflammatory cytokines from a GWAS summary containing 8,293 healthy participants. Causalities of exposures and outcomes were explored mainly using inverse variance weighted method. In addition, multiple sensitivity analyses including MR-Egger, weighted median, simple mode, weighted mode, and MR-PRESSO were simultaneously applied to strengthen the final results.ResultsThe results indicated that cutaneous T cell-attracting chemokine (CTACK) and IL-17 may be suggestively associated with the risk of SLE (odds ratio, OR: 1.21, 95%CI: 1.04–1.41, p = 0.015; OR: 1.37, 95%CI: 1.03–1.82, p = 0.029). In addition, cytokines including beta nerve growth factor, basic fibroblast growth factor, IL-4, IL-6, interferon gamma-induced protein 10, monokine induced by interferon-gamma, MIP1b, stromal cell-derived factor-1 alpha, and tumor necrosis factor-alpha are suggested to be the consequences of SLE disease (Beta: 0.035, p = 0.014; Beta: 0.021, p = 0.032; Beta: 0.024, p = 0.013; Beta: 0.019, p = 0.042; Beta: 0.040, p = 0.005; Beta: 0.046, p = 0.001; Beta: 0.021, p = 0.029; Beta: 0.019, p = 0.045; Beta: 0.029, p = 0.048).ConclusionThis study suggested that CTACK and IL-17 are probably the factors correlated with SLE etiology, while a couple of inflammatory cytokines are more likely to be involved in SLE development downstream.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Here, we performed a MR study to clarify the bidirectional causal association between BMD/fracture and the risk of MS using large-scale publicly available GWAS datasets, as provided in Table 1 . MR has three assumptions: (1) instrumental variables (genetic variants) are strongly associated with an exposure, generally the genome-wide significance ( p <5.00E-08); (2) instrumental variables are independent of confounders; and (3) instrumental variables affect one outcome only via the exposure path ( 24 ).…”

Section: Methodsmentioning

confidence: 99%

Mendelian randomization analysis of the causal association of bone mineral density and fracture with multiple sclerosis

Gao

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

Multiple sclerosis (MS) is a neurodegenerative disorder and an autoimmune disease. Until now, observational studies have indicated the association of bone mineral density (BMD) and fracture with the risk of MS. However, these studies indicated inconsistent findings. Until now, genome-wide association studies (GWAS) have been conducted in BMD, fracture, and MS, which provide large-scale datasets to investigate the causal association of BMD and fracture with the risk of MS using the Mendelian randomization (MR) study. Here, we performed an MR study to clarify the causal association between BMD/fracture and the risk of MS using large-scale publicly available GWAS datasets from BMD, fracture, and MS. We first evaluated the bidirectional causal effects of BMD and MS. The main analysis method inverse-variance weighted (IVW) showed no significant causal effect of BMD on the risk of MS (β = 0.058, and p = 1.98E-01), and MS on the risk of BMD (β = −0.001, and p = 7.83E-01). We then evaluated the bidirectional causal effects of fracture and MS. However, we only identified a significant causal effect of fracture on the risk of MS using IVW (β = −0.375, p = 0.002), but no significant causal effect of MS on the risk of the fracture using IVW (β = 0.011, p = 2.39E-01). Therefore, our main analysis method IVW only found a significant causal effect of fracture on MS using the threshold for the statistically significant association p < 0.05/4 = 0.0125. Meanwhile, multivariable MR analyses showed that the causal effect of fracture on MS was independent of smoking, drinking, and obesity, but dependent on BMD. In summary, our MR analysis demonstrates that genetically increased fracture may reduce the risk of MS. Our findings should be further verified and the underlying mechanisms should be further evaluated by future studies.

show abstract

“…We assessed directional horizontal pleiotropy using the MR-PRESSO global test. Therefore, we interpret the results according to the appropriate MR analysis method [43]. p-value < 0.05 for Cochran's Q statistic, Rücker's Q' statistic, and the MR-PRESSO global test indicate possible pleiotropy in the genetic variations.…”

Section: Mendelian Randomizationmentioning

confidence: 99%

Potential Causal Association between Elevated Gamma-Glutamyl Transferase Level and Stroke: A Two-Sample Mendelian Randomization Study

Lee,

Seo

2023

Biomolecules

View full text Add to dashboard Cite

Researchers have suggested a potential relationship between gamma-glutamyl transferase (GGT) level and stroke. We investigated a potential causal relationship between GGT level as exposures and stroke and stroke subtypes (cardioembolic, small vessel, and large artery) in a European population. We performed a two-sample Mendelian randomization (MR) study using the genome-wide association study (GWAS) data from the UK Biobank as the exposure set. For the outcome set, we used stroke in the GWAS data from the GIGASTROKE Consortium. We considered alcohol consumption, atrial fibrillation, and body mass index as confounders. We used PhenoScanner searches for removal of SNPs and multivariable MR analysis for assessing confounders. We observed significant causal associations between GGT level and stroke (odds ratio [OR] = 1.23, 95% CI = [1.05–1.44], and p = 0.012 with IVW; OR = 1.19, 95% CI= [1.02–1.39], and p = 0.031 with MR-PRESSO). These results were consistent after removing SNPs related to confounding factors. Similarly, in multivariable MR, GGT was associated with stroke after adjusting for confounding factors (OR = 1.30, 95% CI 1.07–1.60), p = 0.010). Because GGT level has a causal relationship with stroke, researchers should test its significance as a potential risk factor for stroke. Additional research is required to validate these results.

show abstract

Causal Evaluation of Laboratory Markers in Type 2 Diabetes on Cancer and Vascular Diseases Using Various Mendelian Randomization Tools

Cited by 23 publications

References 44 publications

Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization

Exploring causal correlations between inflammatory cytokines and systemic lupus erythematosus: A Mendelian randomization

Mendelian randomization analysis of the causal association of bone mineral density and fracture with multiple sclerosis

Potential Causal Association between Elevated Gamma-Glutamyl Transferase Level and Stroke: A Two-Sample Mendelian Randomization Study

Contact Info

Product

Resources

About