A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization study
Abstract Background Previous epidemiological observational studies have indicated an association between type 1 diabetes (T1DM) and systemic sclerosis (SSc). However, the potential causal relationship between T1DM and SSc remains unclear. Therefore, this Mendelian randomization (MR) study aims to in...
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BMC
2025-06-01
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| Series: | Diabetology & Metabolic Syndrome |
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| Online Access: | https://doi.org/10.1186/s13098-025-01743-3 |
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| author | Haochen Huang Bo Yu Fengyun Yu Zhen-zhen Wu Dong Xu Ling-ling Zhang |
| author_facet | Haochen Huang Bo Yu Fengyun Yu Zhen-zhen Wu Dong Xu Ling-ling Zhang |
| author_sort | Haochen Huang |
| collection | DOAJ |
| description | Abstract Background Previous epidemiological observational studies have indicated an association between type 1 diabetes (T1DM) and systemic sclerosis (SSc). However, the potential causal relationship between T1DM and SSc remains unclear. Therefore, this Mendelian randomization (MR) study aims to investigate the bidirectional causal relationship between T1DM and SSc through a bidirectional two-sample mendelian randomization analysis. Methods We utilized SNP data aggregated from previously published genome-wide association studies (GWAS) and selected appropriate SNPs as instrumental variables (IVs). To explore the bidirectional causal relationship between T1DM and SSc, we conducted bidirectional Mendelian randomization analyses using various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode approaches. Additionally, sensitivity analyses were performed to further validate the accuracy of the MR results. Results Our MR analysis using 66 SNPs as IVs for T1DM showed a genetically determined association with an increased risk of SSc (IVW OR = 1.294, 95% CI 1.140–1.469, p < 0.001), consistent across MR-Egger, weighted median, and weighted mode methods, with no evidence of horizontal pleiotropy or heterogeneity, and robustness confirmed by leave-one-out analysis. Conversely, reverse MR analysis using 7 SNPs for SSc revealed no significant association with T1DM (IVW OR = 0.998, 95% CI 0.979–1.016, P = 0.798), consistent across all methods, with no evidence of pleiotropy or heterogeneity, and results confirmed as robust. Conclusion This pioneering mendelian randomization study reveals a causal link between genetic susceptibility to T1DM and an increased risk of SSc, though not vice versa, emphasizing the need for validation across diverse populations and further exploration of underlying mechanisms. |
| format | Article |
| id | doaj-art-5a6f3a6819d34fbeb84ffcd515d69349 |
| institution | Kabale University |
| issn | 1758-5996 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj-art-5a6f3a6819d34fbeb84ffcd515d693492025-08-20T03:25:19ZengBMCDiabetology & Metabolic Syndrome1758-59962025-06-0117111110.1186/s13098-025-01743-3A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization studyHaochen Huang0Bo Yu1Fengyun Yu2Zhen-zhen Wu3Dong Xu4Ling-ling Zhang5Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeSchool of Engineering Medicine, Beihang UniversityKey Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of SciencesDepartment of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical CollegeDepartment of Rheumatology and Clinical Immunology, Beijing Shijitan Hospital, Capital Medical UniversityAbstract Background Previous epidemiological observational studies have indicated an association between type 1 diabetes (T1DM) and systemic sclerosis (SSc). However, the potential causal relationship between T1DM and SSc remains unclear. Therefore, this Mendelian randomization (MR) study aims to investigate the bidirectional causal relationship between T1DM and SSc through a bidirectional two-sample mendelian randomization analysis. Methods We utilized SNP data aggregated from previously published genome-wide association studies (GWAS) and selected appropriate SNPs as instrumental variables (IVs). To explore the bidirectional causal relationship between T1DM and SSc, we conducted bidirectional Mendelian randomization analyses using various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode approaches. Additionally, sensitivity analyses were performed to further validate the accuracy of the MR results. Results Our MR analysis using 66 SNPs as IVs for T1DM showed a genetically determined association with an increased risk of SSc (IVW OR = 1.294, 95% CI 1.140–1.469, p < 0.001), consistent across MR-Egger, weighted median, and weighted mode methods, with no evidence of horizontal pleiotropy or heterogeneity, and robustness confirmed by leave-one-out analysis. Conversely, reverse MR analysis using 7 SNPs for SSc revealed no significant association with T1DM (IVW OR = 0.998, 95% CI 0.979–1.016, P = 0.798), consistent across all methods, with no evidence of pleiotropy or heterogeneity, and results confirmed as robust. Conclusion This pioneering mendelian randomization study reveals a causal link between genetic susceptibility to T1DM and an increased risk of SSc, though not vice versa, emphasizing the need for validation across diverse populations and further exploration of underlying mechanisms.https://doi.org/10.1186/s13098-025-01743-3Autoimmune diseaseMendelian randomizationCausal relationshipType 1 diabetesSystemic sclerosis |
| spellingShingle | Haochen Huang Bo Yu Fengyun Yu Zhen-zhen Wu Dong Xu Ling-ling Zhang A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization study Diabetology & Metabolic Syndrome Autoimmune disease Mendelian randomization Causal relationship Type 1 diabetes Systemic sclerosis |
| title | A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization study |
| title_full | A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization study |
| title_fullStr | A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization study |
| title_full_unstemmed | A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization study |
| title_short | A causal relationship between type 1 diabetes and risk of systemic sclerosis: a bidirectional two-sample Mendelian randomization study |
| title_sort | causal relationship between type 1 diabetes and risk of systemic sclerosis a bidirectional two sample mendelian randomization study |
| topic | Autoimmune disease Mendelian randomization Causal relationship Type 1 diabetes Systemic sclerosis |
| url | https://doi.org/10.1186/s13098-025-01743-3 |
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