Current eye research · 2026
Possible Causal Association Between Thyroid-Related Traits and Diabetic Retinopathy Risk: Evidence From 23 Medication-Taking Traits.
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Xue Zhengbo, Zhang Riyan, Zhang Qinyi, Chen Zhen Ji, Zhang Yue, Qu Jia, Su Jianzhong, Yuan Jian
Аннотация
PURPOSE: To evaluate whether thyroid-related medication-taking traits show evidence consistent with a possible causal relationship for diabetic retinopathy (DR).
METHODS: We utilized genome-wide association study (GWAS) summary statistics from UK Biobank, which included 23 medication-taking traits in a sample of approximately 320,000 individuals and DR data from 1,652 cases and 60,577 controls. We employed Mendelian randomization (MR) approach to investigate the possible causal relationships between medication-taking characteristics and DR. Possible causal effects were screened with TwoSampleMR inverse-variance weighting, confirmed by univariable MR after pleiotropic SNPs were removed via MR-PRESSO; reverse MR excluded reverse causality, and public GWAS data verified the thyroid-disease associations.
RESULTS: We found drugs used in diabetes and thyroid preparations showed a significant association with DR (p < 0.05/22). After removing pleiotropic SNPs, the UVMR analysis suggested a potential relationship between thyroid preparations and DR (IVW: OR = 1.18, p = 1.91 × 10-3). Furthermore, the MR analysis indicated that both hypothyroidism and hyperthyroidism were associated with a significantly higher risk of DR (OR = 1.31, p = 1.75 × 10-6; OR = 1.32, p = 1.05 × 10-4). The findings from different single-nucleotide analytic methods were consistent, suggesting the robustness of the possible causal associations.
CONCLUSIONS: Our findings suggest thyroid dysfunction appears to causally elevate DR risk, informing screening and prevention in diabetes. The precise mechanisms may involve thyroid-related oxidative stress and inflammation.
METHODS: We utilized genome-wide association study (GWAS) summary statistics from UK Biobank, which included 23 medication-taking traits in a sample of approximately 320,000 individuals and DR data from 1,652 cases and 60,577 controls. We employed Mendelian randomization (MR) approach to investigate the possible causal relationships between medication-taking characteristics and DR. Possible causal effects were screened with TwoSampleMR inverse-variance weighting, confirmed by univariable MR after pleiotropic SNPs were removed via MR-PRESSO; reverse MR excluded reverse causality, and public GWAS data verified the thyroid-disease associations.
RESULTS: We found drugs used in diabetes and thyroid preparations showed a significant association with DR (p < 0.05/22). After removing pleiotropic SNPs, the UVMR analysis suggested a potential relationship between thyroid preparations and DR (IVW: OR = 1.18, p = 1.91 × 10-3). Furthermore, the MR analysis indicated that both hypothyroidism and hyperthyroidism were associated with a significantly higher risk of DR (OR = 1.31, p = 1.75 × 10-6; OR = 1.32, p = 1.05 × 10-4). The findings from different single-nucleotide analytic methods were consistent, suggesting the robustness of the possible causal associations.
CONCLUSIONS: Our findings suggest thyroid dysfunction appears to causally elevate DR risk, informing screening and prevention in diabetes. The precise mechanisms may involve thyroid-related oxidative stress and inflammation.