Dataset Information

[Type 1 diabetes mellitus is likely to increase the risk of thyrotoxicdsis: a two-sample Mendelian randomization study].

ABSTRACT:

Objective

To explore the relationship between type 1 diabetes (T1DM) and thyrotoxicosis using two-sample Mendelian randomization (MR) method.

Methods

Based on the data from a large-scale metabolome-based genome-wide association study (GWAS), we investigated the causality between T1DM and thyrotoxicosis using inverse variance-weighted (IVW) method, MR-Egger regression, weighted Mode (WM) method and weighted median (WME) method. Single nucleotide polymorphisms (SNPs) closely related to T1DM were screened as the instrumental variables (IVs). Outlier testing was performed using MR-PRESSON to reject the outliers. Heterogeneity tests, horizontal pleiotropy and sensitivity tests were performed to evaluate the reliability and stability of the results, and F-values were calculated to assess the presence of weak IVs bias.

Results

There was a positive causal effect between T1DM and thyrotoxicosis in the total samples analyzed with the 4 MR methods. The ORs and 95% CIs calculated by IVW, MR-Egger regression, WM and WME methods were 1.077 (95% CI: 1.046-1.109), 1.076 (95% CI: 1.031-1.124), 1.082 (95% CI: 1.048-1.118), and 1.090 (95% CI: 1.052-1.129), respectively. The results of the heterogeneity test were P=0.127 and P=0.155, respectively, suggesting the absence of heterogeneity. Egger-intercept result was P=0.965, indicating the absence of pleiotropy. Leave-one-out analysis showed stable results. All the F values were greater than 10, indicating that there was no weak IVs bias.

Conclusion

T1DM is likely to increase the risk of thyrotoxicosis.

SUBMITTER: Zhan W

PROVIDER: S-EPMC10505565 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

[Type 1 diabetes mellitus is likely to increase the risk of thyrotoxicdsis: a two-sample Mendelian randomization study].

Zhan W W Zhao L L

Nan fang yi ke da xue xue bao = Journal of Southern Medical University 20230801 8

<h4>Objective</h4>To explore the relationship between type 1 diabetes (T1DM) and thyrotoxicosis using two-sample Mendelian randomization (MR) method.<h4>Methods</h4>Based on the data from a large-scale metabolome-based genome-wide association study (GWAS), we investigated the causality between T1DM and thyrotoxicosis using inverse variance-weighted (IVW) method, MR-Egger regression, weighted Mode (WM) method and weighted median (WME) method. Single nucleotide polymorphisms (SNPs) closely related ...[more]

PMID: 37712277

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Project description:BackgroundGestational diabetes mellitus (GDM) constitutes a significant contributor to maternal and fetal morbidity, which is observed to be associated with future risks of offspring health. Nevertheless, it is essential to acknowledge that observational findings may be susceptible to residual confounding and bias.MethodsTo investigate the association of GDM with offspring health, a genome-wide genetic association study employing Mendelian Randomization (MR) is conducted between May 31 and November 30, 2023. The inverse-variance-weighted (IVW) is utilized in the primary analysis stage. The study data of the majority patients are European ancestry, which are sourced from the IEU open genome-wide association study project.ResultsGenetically predicted GDM is associated with an increased risk of various short- and long-term health problem in offspring. For fetal and neonatal conditions, GDM is linked to an elevated risk of preterm delivery [ odd ratio (OR) = 1.150, false discovery rate (FDR)-adjusted PIVW = 0.009] and placental disorders (OR = 2.143, FDR-adjusted PIVW = 0.028). In respiratory diseases, it is associated with a higher likelihood of influenza (OR = 1.175, FDR-adjusted PIVW = 0.008), bacterial pneumonia (OR = 1.141, FDR-adjusted PIVW = 0.008), congenital malformations of the respiratory system (OR = 1.673, FDR-adjusted PIVW = 0.033), influenza with pneumonia (OR = 1.078, FDR-adjusted PIVW = 0.008), and need for non-invasive ventilation (OR = 1.265, FDR-adjusted PIVW = 0.028). In terms of neurodevelopmental and psychiatric outcomes, GDM is linked to a higher risk of cerebral palsy (OR = 1.721, FDR-adjusted PIVW = 0.008). For urinary conditions, GDM increases the risk of acute tubulo-interstitial nephritis (OR = 1.098, FDR-adjusted PIVW = 0.008). No association is identified between genetically predicted GDM and major digestive diseases, such as gastroesophageal reflux, or cardiovascular conditions in offspring.ConclusionsThe findings of this study provide genetic evidence supporting an association between GDM and higher risk of offspring diseases. This supports classification of GDM as risk factors for short- and long-term offspring health.

Project description:PurposeType 1 diabetes mellitus (T1DM) is associated with different types of infections; however, studies on the causal relationship between T1DM and infectious diseases are lacking. Therefore, our study aimed to explore the causalities between T1DM and six high-frequency infections using a Mendelian randomization (MR) approach.MethodsTwo-sample MR studies were conducted to explore the causalities between T1DM and six high-frequency infections: sepsis, acute lower respiratory infections (ALRIs), intestinal infections (IIs), infections of the genitourinary tract (GUTIs) in pregnancy, infections of the skin and subcutaneous tissues (SSTIs), and urinary tract infections (UTIs). Data on summary statistics for T1DM and infections were obtained from the European Bioinformatics Institute database, the United Kingdom Biobank, FinnGen biobank, and Medical Research Council Integrative Epidemiology Unit. All data obtained for summary statistics were from European countries. The inverse-variance weighted (IVW) method was employed as the main analysis. Considering the multiple comparisons, statistical significance was set at p< 0.008. If univariate MR analyses found a significant causal association, multivariable MR (MVMR) analyses were performed to adjust body mass index (BMI) and glycated hemoglobin (HbA1c). MVMR-IVW was performed as the primary analysis, and the least absolute shrinkage and selection operator (LASSO) regression and MVMR-Robust were performed as complementary analyses.ResultsMR analysis showed that susceptibility to IIs increased in patients with T1DM by 6.09% using the IVW-fixed method [odds ratio (OR)=1.0609; 95% confidence interval (CI): 1.0281-1.0947, p=0.0002]. Results were still significant after multiple testing. Sensitivity analyses did not show any significant horizontal pleiotropy or heterogeneity. After adjusting for BMI and HbA1c, MVMR-IVW (OR=1.0942; 95% CI: 1.0666-1.1224, p<0.0001) showed significant outcomes that were consistent with those of LASSO regression and MVMR-Robust. However, no significant causal relationship was found between T1DM and sepsis susceptibility, ALRI susceptibility, GUTI susceptibility in pregnancy, SSTI susceptibility, and UTI susceptibility.ConclusionsOur MR analysis genetically predicted increased susceptibility to IIs in T1DM. However, no causality between T1DM and sepsis, ALRIs, GUTIs in pregnancy, SSTIs, or UTIs was found. Larger epidemiological and metagenomic studies are required to further investigate the observed associations between the susceptibility of certain infectious diseases with T1DM.

Dataset Information

[Type 1 diabetes mellitus is likely to increase the risk of thyrotoxicdsis: a two-sample Mendelian randomization study].

Objective

Methods

Results

Conclusion

Publications

[Type 1 diabetes mellitus is likely to increase the risk of thyrotoxicdsis: a two-sample Mendelian randomization study].

Similar Datasets

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