Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study
BackgroundGraves’ disease (GD) is an autoimmune disease associated with an increased incidence of other autoimmune diseases. To investigate the causality between GD and Diabetes mellitus (DM), we designed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) studies.Metho...
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Frontiers Media S.A.
2024-11-01
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| author | Yuhan Zhang Yuhan Zhang Yuhan Zhang Liuxiang Fu |
| author_facet | Yuhan Zhang Yuhan Zhang Yuhan Zhang Liuxiang Fu |
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| description | BackgroundGraves’ disease (GD) is an autoimmune disease associated with an increased incidence of other autoimmune diseases. To investigate the causality between GD and Diabetes mellitus (DM), we designed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) studies.MethodsSingle-nucleotide polymorphisms (SNPs) associated with GD, thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), type 1 diabetes (T1D), and type 2 diabetes (T2D) were obtained from the IEU Open GWAS and FinnGen biobank databases. For the forward MR study, we used GD (sample size = 458,620) as the exposure and T1D (sample size = 520,580) and T2D (sample size = 211,766) as the outcomes. Next, high risk of T1D and T2D were used as exposure variables, and GD was used as the outcome variable for the reverse MR analysis. Finally, MVMR analysis was conducted to investigate the probable relationship between DM and indicators for thyroid function like TPO, Tg, and TSH. The inverse variance weighting (IVW) was used as the main method. Finally, the heterogeneity and sensitivity were assessed.ResultsThere were 27, 88, and 55 SNPs associated with GD, T1D, and T2D, respectively. A significant causal connection between higher genetic liability of GD and the risk of T2D (OR [95% CI] = 1.059 [1.025–1.095], P = 5.53e-04) was found in the forward MR analysis. Comparatively, the significant causal relationship between higher genetic liability of GD and the risk of T1D was not demonstrated (OR [95% CI] = 0.998[0.927,1.074], P=0.949). However, reverse MR suggested that there was a genetic susceptibility to T1D that increased the likelihood of developing GD (OR [95% CI] = 1.173[1.117,1.231], P = 1.913e-10), while T2D did not (OR [95% CI] = 0.963 [0.870–1.066], P = 0.468). Furthermore, there was inadequate evidence to suggest that abnormal TSH, TPO, and Tg levels increase the risk of incident T1D or T2D in individuals with GD. MVMR revealed no causal relationship among Tg, TSH, TPO, T1D, or T2D.ConclusionThere was no increased risk of T1D with an increase in genetic susceptibility to GD, although higher genetic susceptibility to T1D has been shown to be associated with increased risk of developing GD. A unidirectional causal relationship between the genetic liability for GD and increased risk of T2D was observed using MR analyses. MVMR analysis showed no statistically relevant causality between the genetic liability for TSH, TPO, or Tg and the risk of either T1D or T2D. |
| format | Article |
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| institution | OA Journals |
| issn | 1664-2392 |
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| spelling | doaj-art-efb0108147124fef8c48ff2e5c049cef2025-08-20T02:12:37ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922024-11-011510.3389/fendo.2024.14204991420499Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization studyYuhan Zhang0Yuhan Zhang1Yuhan Zhang2Liuxiang Fu3Emergency Department, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1 Minde Road, Nanchang, ChinaGeneral Surgery Center, Department of Thyroid Surgery, The 1st Hospital of Jilin University, Chang Chun, ChinaDepartment of General Surgery, Panzhihua Central Hospital, Panzhihua, ChinaEmergency Department, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No.1 Minde Road, Nanchang, ChinaBackgroundGraves’ disease (GD) is an autoimmune disease associated with an increased incidence of other autoimmune diseases. To investigate the causality between GD and Diabetes mellitus (DM), we designed bidirectional two-sample Mendelian randomization (MR) and multivariable MR (MVMR) studies.MethodsSingle-nucleotide polymorphisms (SNPs) associated with GD, thyroid peroxidase (TPO), thyroglobulin (Tg), thyroid-stimulating hormone (TSH), type 1 diabetes (T1D), and type 2 diabetes (T2D) were obtained from the IEU Open GWAS and FinnGen biobank databases. For the forward MR study, we used GD (sample size = 458,620) as the exposure and T1D (sample size = 520,580) and T2D (sample size = 211,766) as the outcomes. Next, high risk of T1D and T2D were used as exposure variables, and GD was used as the outcome variable for the reverse MR analysis. Finally, MVMR analysis was conducted to investigate the probable relationship between DM and indicators for thyroid function like TPO, Tg, and TSH. The inverse variance weighting (IVW) was used as the main method. Finally, the heterogeneity and sensitivity were assessed.ResultsThere were 27, 88, and 55 SNPs associated with GD, T1D, and T2D, respectively. A significant causal connection between higher genetic liability of GD and the risk of T2D (OR [95% CI] = 1.059 [1.025–1.095], P = 5.53e-04) was found in the forward MR analysis. Comparatively, the significant causal relationship between higher genetic liability of GD and the risk of T1D was not demonstrated (OR [95% CI] = 0.998[0.927,1.074], P=0.949). However, reverse MR suggested that there was a genetic susceptibility to T1D that increased the likelihood of developing GD (OR [95% CI] = 1.173[1.117,1.231], P = 1.913e-10), while T2D did not (OR [95% CI] = 0.963 [0.870–1.066], P = 0.468). Furthermore, there was inadequate evidence to suggest that abnormal TSH, TPO, and Tg levels increase the risk of incident T1D or T2D in individuals with GD. MVMR revealed no causal relationship among Tg, TSH, TPO, T1D, or T2D.ConclusionThere was no increased risk of T1D with an increase in genetic susceptibility to GD, although higher genetic susceptibility to T1D has been shown to be associated with increased risk of developing GD. A unidirectional causal relationship between the genetic liability for GD and increased risk of T2D was observed using MR analyses. MVMR analysis showed no statistically relevant causality between the genetic liability for TSH, TPO, or Tg and the risk of either T1D or T2D.https://www.frontiersin.org/articles/10.3389/fendo.2024.1420499/fullGraves’ diseaseMendelian randomizationtype 1 diabetestype 2 diabetesautoimmune disease |
| spellingShingle | Yuhan Zhang Yuhan Zhang Yuhan Zhang Liuxiang Fu Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study Frontiers in Endocrinology Graves’ disease Mendelian randomization type 1 diabetes type 2 diabetes autoimmune disease |
| title | Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study |
| title_full | Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study |
| title_fullStr | Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study |
| title_full_unstemmed | Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study |
| title_short | Evaluating the causal effects between Grave’s disease and diabetes mellitus: a bidirectional Mendelian randomization study |
| title_sort | evaluating the causal effects between grave s disease and diabetes mellitus a bidirectional mendelian randomization study |
| topic | Graves’ disease Mendelian randomization type 1 diabetes type 2 diabetes autoimmune disease |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2024.1420499/full |
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