甲状腺功能障碍与糖尿病视网膜病变之间的关联：一项两样本双向孟德尔随机化研究。
Association between thyroid dysfunction and diabetic retinopathy: a two-sample bidirectional Mendelian randomization study.
作者信息
Chen Jiali, Xiong Jianghao, Zhang Fenfen, Pan Wanyu, Cheng Shaomin
机构信息
School of Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330000, Jiangxi, China.
Department of Respiratory and Critical Care Medicine, Jiangxi Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Nanchang, 330000, Jiangxi, China.
出版信息
Diabetol Metab Syndr. 2024 Dec 18;16(1):297. doi: 10.1186/s13098-024-01552-0.
OBJECTIVES
To assess the association between thyroid dysfunction and diabetic retinopathy (DR), a two-sample bidirectional Mendelian randomization (MR) study utilizing the Genome-wide Association Study (GWAS) database was conducted to investigate the causal relationship between these two variables.
METHODS
In this study, GWAS of 48,328,151 single nucleotide polymorphisms(SNP) in the European population from the IEU open GWAS database were utilized as genetic tools for investigating thyroid dysfunction. The total sample size for the study on hyperthyroidism was 460,499 (case group: 3557; control group: 456,942). The total sample size for hypothyroidism was 410,141 (case group: 30,155; control group: 37,986). In addition, the data on DR were extracted from the FinnGen Biobank, comprising a total sample size of 319,046 individuals (10,413 cases and 308,633 controls). For the forward MR analysis, hyperthyroidism and hypothyroidism were considered as exposures with DR as the outcome. Reverse MR analysis was conducted using DR as exposure and hyperthyroidism and hypothyroidism as outcomes.
METHODS
The main analytical approach employed inverse variance weighting(IVW), supplemented by MR-Egger, Weighted mode method, weighted median, and Simple mode. Cochran's Q test, MR-PRESSO, MR-Egger and leave-one-out analysis were used to evaluate the sensitivity and pleiotropy.
RESULTS
Two-sample bidirectional MR analysis revealed a significant association between the presence of hyperthyroidism and hypothyroidism and an increased risk of DR in the forward MR analysis (IVW: OR = 1.29, 95% [CI] = 1.12-1.49, P < 0.001; OR = 1.17, 95% CI = 1.10-1.25, P < 0.001). In the reverse MR analysis, DR was found to be associated with an elevated risk of developing hyperthyroidism and hypothyroidism (IVW: OR = 1.56, 95% CI 1.38-1.76, P < 0.001; OR = 1.41, 95% CI 1.25-1.59, P < 0.001). Furthermore, most supplementary MR methods also demonstrated statistically significant differences and exhibited effect sizes consistent with those obtained from IVW. The sensitivity analysis confirmed the relative reliability of our causal findings.
CONCLUSIONS
Our findings provide genetic evidence supporting a bidirectional causal relationship between thyroid function and DR.
目的
为评估甲状腺功能障碍与糖尿病视网膜病变（DR）之间的关联，开展了一项利用全基因组关联研究（GWAS）数据库的两样本双向孟德尔随机化（MR）研究，以探究这两个变量之间的因果关系。
方法
在本研究中，来自IEU开放GWAS数据库的欧洲人群中48328151个单核苷酸多态性（SNP）的GWAS被用作研究甲状腺功能障碍的遗传工具。甲状腺功能亢进症研究的总样本量为460499（病例组：3557；对照组：456942）。甲状腺功能减退症的总样本量为410141（病例组：30155；对照组：37986）。此外，DR的数据从芬兰生物银行提取，总样本量为319046人（10413例病例和308633例对照）。在前向MR分析中，甲状腺功能亢进症和甲状腺功能减退症被视为暴露因素，DR作为结果。以DR为暴露因素，甲状腺功能亢进症和甲状腺功能减退症为结果进行反向MR分析。
方法
主要分析方法采用逆方差加权（IVW），辅以MR-Egger、加权模式法、加权中位数和简单模式。使用Cochran's Q检验、MR-PRESSO、MR-Egger和留一法分析来评估敏感性和多效性。
结果
两样本双向MR分析显示，在前向MR分析中，甲状腺功能亢进症和甲状腺功能减退症的存在与DR风险增加之间存在显著关联（IVW：OR = 1.29，95%[CI]=1.12 - 1.49，P < 0.001；OR = 1.17，95%CI = 1.10 - 1.25，P < 0.001）。在反向MR分析中，发现DR与甲状腺功能亢进症和甲状腺功能减退症发生风险升高相关（IVW：OR = 1.56，95%CI 1.38 - 1.76，P < 0.001；OR = 1.41，95%CI 1.25 - 1.59，P < 0.001）。此外，大多数补充MR方法也显示出统计学上的显著差异，并且效应大小与IVW获得的结果一致。敏感性分析证实了我们因果关系研究结果的相对可靠性。
结论
我们的研究结果提供了遗传证据，支持甲状腺功能与DR之间的双向因果关系。
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