孟德尔随机化
医学
孟德尔遗传
人口
随机化
人口学
遗传学
内科学
儿科
生物信息学
生物
随机对照试验
基因型
环境卫生
基因
遗传变异
社会学
作者
Shu Liu,Qiang Sun,Qing-Wei Gu,Yu-Jie Bao,Wei Wang,Xiaodong Qin,Xinran Yuan
标识
DOI:10.3389/fendo.2024.1254793
摘要
Objective To determine whether there is a causal relationship between thyroid dysfunction and the risk of age-related cataract (ARC) in the European population. Design A two-sample Mendelian randomization (MR) study. Methods Hypothyroidism, hyperthyroidism, free thyroxine (fT4), and thyrotropin (TSH) were selected as exposures. The single nucleotide polymorphisms (SNP) of hypothyroidism and hyperthyroidism were obtained from the genome-wide association studies (GWAS) of the IEU database, including 337,159 subjects. Data for fT4 and TSH (72,167 subjects) were extracted from the ThyroidOmics Consortium. ARC was used as the outcome. The SNPs associated with ARC were selected from a GWAS of 216,362 individuals in the FinnGen database. The main method used was the inverse variance-weighted method, together with four complementary methods. Sensitivity analyses were performed using Cochran’s Q test, MR-PRESSO, MR-Egger regression and leave-one-out test. MR pleiotropy was used to test for pleiotropy. MR Steiger test was used to test for the directionality. Results Two-sample MR analysis revealed a positive association between genetically predicted hypothyroidism and risk of ARC (OR = 2.501, 95% CI: 1.325-4.720; P = 0.004). Hyperthyroidism, circulating fT4 and TSH levels did not have a significant causal effect on ARC ( P > 0.05). The results were robust and reliable, and no horizontal pleiotropy was found after sensitivity analyses. In the MR Steiger test, we found no reverse causal effects of hypothyroidism on the ARC ( P < 0.001). Conclusions Our study provides strong evidence that hypothyroidism is a causal determinant of ARC risk.
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