目的 使用孟德尔随机化(MR)探索甲状腺疾病与泌尿系结石之间的因果关系。方法 利用来自大型全基因组关联研究(GWAS)收集甲状腺功能亢进、甲状腺功能减退、甲状腺癌、促甲状腺激素(TSH)、游离四碘甲状腺原氨酸(FT4)、游离三碘甲状腺原氨酸/游离四碘甲状腺原氨酸(FT3/FT4)和泌尿系结石的数据,进行两样本MR研究。研究中纳入欧洲患者人群数据,采用逆方差加权法(IVW)、MR-Egger 回归法、加权中位数法、加权众数法评估甲状腺疾病和泌尿系结石之间的关联,通过Cochran’s检验评估异质性,使用MR-Egger截距检验评估水平多效性,利用MR-PRESSO方法探测并纠正可能的异常工具变量。结果 IVW法分析显示,甲状腺功能减退与泌尿系结石呈负向因果关系,甲状腺功能减退可以降低泌尿系结石的发生风险(OR=0.939,95%CI=0.8823~0.9993,P=0.047),甲状腺功能亢进、甲状腺癌、血清TSH、FT4、FT3/FT4与泌尿系结石的发生无因果关系,未观察到显著异质性和水平多样性。结论 甲状腺功能减退与泌尿系结石之间存在潜在的因果关系。
Abstract
Objective To explore the causal relationship between thyroid disorders and urolithiasis through Mendelian randomization (MR). Methods Data on hyperthyroidism, hypothyroidism, thyroid cancer, thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine/free thyroxine (FT3/FT4), and urolithiasis were collected from large-scale genome-wide association studies (GWAS). A two-sample MR analysis was conducted. The study included data from individuals of European ancestry. Causal associations between thyroid disorders and urolithiasis were assessed using inverse variance weighting (IVW), MR-Egger regression, weighted median, and weighted mode methods. Cochran’s test was used to evaluate heterogeneity, and the MR-Egger intercept test was applied to assess horizontal pleiotropy. The MR-PRESSO method was employed to detect and correct potential outlier instrumental variables. Results The IVW method showed a negative causal relationship between hypothyroidism and urolithiasis, indicating that hypothyroidism could reduce the risk of urolithiasis (OR=0.939, 95% CI=0.8823-0.9993, P=0.047). No causal associations were observed between hyperthyroidism, thyroid cancer, serum TSH, FT4, FT3/FT4 and the risk of urolithiasis. No significant heterogeneity or horizontal pleiotropy was detected. Conclusions There is a potential causal relationship between hypothyroidism and urolithiasis.
关键词
泌尿系结石 /
甲状腺功能减退 /
甲状腺功能亢进 /
孟德尔随机化 /
因果关系
Key words
urolithiasis /
hypothyroidism /
hyperthyroidism /
Mendelian randomization /
causal relationship
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基金
安徽中医药大学2024年度临床科研项目(2024LC060)
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