Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome
Abstract Background Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. Methods We performed a two-sample Mendelian randomization (MR) analysi...
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BMC
2023-11-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-023-00550-z |
| _version_ | 1797557786506166272 |
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| author | Shuwen Chen Zaixin Guo Qi Yu |
| author_facet | Shuwen Chen Zaixin Guo Qi Yu |
| author_sort | Shuwen Chen |
| collection | DOAJ |
| description | Abstract Background Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. Methods We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis. Conclusion This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary. |
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| language | English |
| last_indexed | 2024-03-10T17:21:07Z |
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| spelling | doaj.art-24c3b6089f2242f4b121b4b1f7b48d522023-11-20T10:18:46ZengBMCHuman Genomics1479-73642023-11-0117111510.1186/s40246-023-00550-zGenetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndromeShuwen Chen0Zaixin Guo1Qi Yu2Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus)Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus)Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Peking Union Medical College Hospital (Dongdan Campus)Abstract Background Accumulating observational studies have identified associations between type 1 diabetes (T1D) and polycystic ovary syndrome (PCOS). Still, the evidence about the causal effect of this association is uncertain. Methods We performed a two-sample Mendelian randomization (MR) analysis to test for the causal association between T1D and PCOS using data from a large-scale biopsy-confirmed genome-wide association study (GWAS) in European ancestries. We innovatively divided T1D into nine subgroups to be analyzed separately, including: type1 diabetes wide definition, type1 diabetes early onset, type 1 diabetes with coma, type 1 diabetes with ketoacidosis, type 1 diabetes with neurological complications, type 1 diabetes with ophthalmic complications, type 1 diabetes with peripheral circulatory complications, type 1 diabetes with renal complications, and type 1 diabetes with other specified/multiple/unspecified complications. GWAS data for PCOS were obtained from a large-scale GWAS (10,074 cases and 103,164 controls) for primary analysis and the IEU consortium for replication and meta-analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Results Following rigorous instrument selection steps, the number of SNPs finally used for T1D nine subgroups varying from 6 to 36 was retained in MR estimation. However, we did not observe evidence of causal association between type 1 diabetes nine subgroups and PCOS using the IVW analysis, MR-Egger regression, and weighted median approaches, and all P values were > 0.05 with ORs near 1. Subsequent replicates and meta-analyses also yielded consistent results. A number of sensitivity analyses also did not reveal heterogeneity and pleiotropy, including Cochran’s Q test, MR-Egger intercept test, MR-PRESSO global test, leave-one-out analysis, and funnel plot analysis. Conclusion This is the first MR study to investigate the causal relationship between type 1 diabetes and PCOS. Our findings failed to find substantial causal effect of type 1 diabetes on risk of PCOS. Further randomized controlled studies and MR studies are necessary.https://doi.org/10.1186/s40246-023-00550-zType 1 diabetes (T1D)Polycystic ovary syndrome (PCOS)Mendelian randomization (MR)Causal effectGenetic epidemiology |
| spellingShingle | Shuwen Chen Zaixin Guo Qi Yu Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome Human Genomics Type 1 diabetes (T1D) Polycystic ovary syndrome (PCOS) Mendelian randomization (MR) Causal effect Genetic epidemiology |
| title | Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome |
| title_full | Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome |
| title_fullStr | Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome |
| title_full_unstemmed | Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome |
| title_short | Genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome |
| title_sort | genetic evidence for the causal association between type 1 diabetes and the risk of polycystic ovary syndrome |
| topic | Type 1 diabetes (T1D) Polycystic ovary syndrome (PCOS) Mendelian randomization (MR) Causal effect Genetic epidemiology |
| url | https://doi.org/10.1186/s40246-023-00550-z |
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