Causal relationship between type 1 diabetes mellitus and six high-frequency infectious diseases: A two-sample mendelian randomization study

Chen, Xiaohong; Liu, Hong-Qiong; Nie, Qiong; Wang, Han; Xiang, Tao

doi:10.3389/fendo.2023.1135726

Cited by 5 publications

(4 citation statements)

References 61 publications

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“…The MR-PRESSO was implemented to identify and remove pleiotropic outliers so that the causal impact estimate is obtained (39). Considering the multiple comparisons, the Bonferroni method was performed to rectify overall type I errors, and p<0.01 (0.05/5) was considered statistically significant association, while p<0.05 was considered suggestive association (22,40).…”

Section: Discussionmentioning

confidence: 99%

Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian randomization study in Europeans and East Asians

Zhao,

Li,

Shi

et al. 2024

Front. Endocrinol.

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ObjectiveMultiple observational studies have demonstrated an association between type 2 diabetes mellitus (T2DM) and chronic liver diseases (CLDs). However, the causality of T2DM on CLDs remained unknown in various ethnic groups.MethodsWe obtained instrumental variables for T2DM and conducted a two-sample mendelian randomization (MR) study to examine the causal effect on nonalcoholic fatty liver disease (NAFLD), hepatocellular carcinoma (HCC), viral hepatitis, hepatitis B virus (HBV) infection, and hepatitis C virus (HCV) infection risk in Europeans and East Asians. The primary analysis utilized the inverse variance weighting (IVW) technique to evaluate the causal relationship between T2DM and CLDs. In addition, we conducted a series of rigorous analyses to bolster the reliability of our MR results.ResultsIn Europeans, we found that genetic liability to T2DM has been linked with increased risk of NAFLD (IVW : OR =1.3654, 95% confidence interval [CI], 1.2250-1.5219, p=1.85e-8), viral hepatitis (IVW : OR =1.1173, 95%CI, 1.0271-1.2154, p=0.0098), and a suggestive positive association between T2DM and HCC (IVW : OR=1.2671, 95%CI, 1.0471-1.5333, p=0.0150), HBV (IVW : OR=1.1908, 95% CI, 1.0368-1.3677, p=0.0134). No causal association between T2DM and HCV was discovered. Among East Asians, however, there was a significant inverse association between T2DM and the proxies of NAFLD (ALT: IVW OR=0.9752, 95%CI 0.9597-0.9909, p=0.0021; AST: IVW OR=0.9673, 95%CI, 0.9528-0.9821, p=1.67e-5), and HCV (IVW: OR=0.9289, 95%CI, 0.8852-0.9747, p=0.0027). Notably, no causal association was found between T2DM and HCC, viral hepatitis, or HBV.ConclusionOur MR analysis revealed varying causal associations between T2DM and CLDs in East Asians and Europeans. Further research is required to investigate the potential mechanisms in various ethnic groups, which could yield new insights into early screening and prevention strategies for CLDs in T2DM patients.

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Section: Discussionmentioning

confidence: 99%

Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian randomization study in Europeans and East Asians

Zhao,

Li,

Shi

et al. 2024

Front. Endocrinol.

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“…However, after adjusting for BMI and smoking, this relationship lost statistical significance, aligning with previous MR studies. 36 This may suggest that T1D is not responsible for susceptibility to sepsis.…”

Section: Discussionmentioning

confidence: 99%

Unravelling the Link Between Primary Sclerosing Cholangitis and Sepsis: A Mendelian Randomization Study

Chen,

Wu,

et al. 2024

Preprint

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Background: autoimmune diseases (ADS) are associated with sepsis. This study aims to investigate the causalities between ADs and sepsis using Mendelian randomization (MR). Methods: we extracted single-nucleotide polymorphisms (SNPs) closely associated with 10 ADs, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS), inflammatory bowel disease (IBD), celiac disease (CD), psoriasis (PsO), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), and ulcerative colitis (UC) from the GWAS. Two-sample MR analysis was conducted using GWAS data from the UK Biobank to assess the association between the liability of each ad and sepsis and sepsis-related 28-day mortality. The inverse variance-weighted (IVW) method was used as the primary analysis. If sig-nificant causal relationships are found (considering multiple comparisons) in the univariate MR analysis, multivariate MR (MVMR) analysis is performed to adjust for body mass index (BMI) and smoking. A series of sensitivity analyses were conducted to validate the robustness of the results. Results: after adjusting for multiple testing, MR analysis revealed that PSC patients are responsible for increased susceptibility to sepsis using the IVW method (OR:1.033, 95%CI:1.007-1.060, PFDR = 0.020). Further sensitivity analyses validated the robustness of the above association. Even after adjusting for BMI and smoking, the MVMR-IVW still displayed a positive correlation（OR:1.043, 95%CI:1.022-1.064, P-value for IVW = 3.32E-05） between PSC patients and susceptibility to sepsis. However, no significant causal relationship was observed between SLE, RA, T1D, MS, IBD, CD, PsO, PBC, and UC with susceptibility to sepsis or short-term death risk. Conclusions: our MR analysis revealed a genetic susceptibility of PSC to sepsis. However, no causal relationship was observed between SLE, RA, T1D, MS, IBD, CD, PsO, PBC, and UC with suscep-tibility to sepsis or short-term death risk. Keywords: autoimmune diseases; sepsis; primary sclerosing cholangitis; Mendelian randomization

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“…Genetic variations linked to T1DM were sourced from the European Bioinformatics Institute (EBI) database ( 11 ). Data on candidiasis, aspergillosis, pneumocystis, and other mycoses were acquired from the FinnGen Consortium ( 12 ), involving participants.…”

Section: Methodsmentioning

confidence: 99%

Causal relationship between type 1 diabetes mellitus and mycoses: a Mendelian randomization study

Chen,

et al. 2024

Front. Med.

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BackgroundType 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses.MethodsGenetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy.ResultsGenetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02–1.07, p = 0.0001), with a Bonferroni-adjusted p-value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03–1.13, p = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02–1.06, p = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis.ConclusionThis MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.

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Causal relationship between type 1 diabetes mellitus and six high-frequency infectious diseases: A two-sample mendelian randomization study

Cited by 5 publications

References 61 publications

Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian randomization study in Europeans and East Asians

Associations between type 2 diabetes mellitus and chronic liver diseases: evidence from a Mendelian randomization study in Europeans and East Asians

Unravelling the Link Between Primary Sclerosing Cholangitis and Sepsis: A Mendelian Randomization Study

Causal relationship between type 1 diabetes mellitus and mycoses: a Mendelian randomization study

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