Qiu Shizheng, Cao Peigang, Guo Yu, Lu Haoyu, Hu Yang
School of Life Sciences and Technology, Harbin Institute of Technology, Harbin, China.
Department of Cardiovascular, General Hospital of Heilongjiang Province Land Reclamation Bureau, Harbin, China.
Front Cell Dev Biol. 2021 Mar 15;9:643582. doi: 10.3389/fcell.2021.643582. eCollection 2021.
The etiology of non-alcoholic fatty liver disease (NAFLD) involves complex interaction of genetic and environmental factors. A large number of observational studies have shown that hypothyroidism contributes to a high risk of NAFLD. However, the exact causality is still unknown. Due to the progress of genome-wide association study (GWAS) and the discovery of Mendelian randomization (MR), it is possible to explore the causality between the two diseases. In this study, in order to research into the influence of intermediate phenotypes on outcome, nine independent genetic variants of hypothyroidism obtained from the GWAS were used as instrumental variables (IVs) to perform MR analysis on NAFLD. Since there was no heterogeneity between IVs ( = 0.70), a fixed-effects model was used. The correlation between hypothyroidism and NAFLD was evaluated by using inverse-variance weighted (IVW) method and weighted median method. Then the sensitivity test was analyzed. The results showed that there was a high OR (1.7578; 95%CI 1.1897-2.5970; = 0.0046) and a low intercept (-0.095; = 0.431). None of the genetic variants drove the overall result ( < 0.01). Simply, we proved for the first time that the risk of NAFLD increases significantly on patients with hypothyroidism. Furthermore, we explained possible causes of NAFLD caused by hypothyroidism.
非酒精性脂肪性肝病（NAFLD）的病因涉及遗传和环境因素的复杂相互作用。大量观察性研究表明，甲状腺功能减退会导致NAFLD的高风险。然而，确切的因果关系仍然未知。由于全基因组关联研究（GWAS）的进展以及孟德尔随机化（MR）的发现，有可能探索这两种疾病之间的因果关系。在本研究中，为了研究中间表型对结果的影响，从GWAS中获得的9个甲状腺功能减退的独立基因变异被用作工具变量（IVs），对NAFLD进行MR分析。由于IVs之间不存在异质性（I² = 0.70），因此使用固定效应模型。采用逆方差加权（IVW）法和加权中位数法评估甲状腺功能减退与NAFLD之间的相关性。然后进行敏感性检验。结果显示，OR值较高（1.7578；95%CI 1.1897 - 2.5970；P = 0.0046），截距较低（-0.095；P = 0.431）。没有一个基因变异驱动总体结果（P < 0.01）。简而言之，我们首次证明甲状腺功能减退患者患NAFLD的风险显著增加。此外，我们解释了甲状腺功能减退导致NAFLD的可能原因。
