Department of Endocrinology and Metabolism and the institute of Endocrinology, The First Hospital of China Medical University, Shenyang, Liaoning, 110001, P.R. China.
J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4251-e4259. doi: 10.1210/clinem/dgab183.
The association between serum thyrotropin (TSH) and obesity traits has been investigated previously in several epidemiological studies. However, the underlying causal association has not been established.
This work aimed to determine and analyze the causal association between serum TSH level and obesity-related traits (body mass index [BMI] and obesity).
The latest genome-wide association studies (GWASs) on TSH, BMI, and obesity were searched to obtain full statistics. Bidirectional 2-sample mendelian randomization (MR) was performed to explore the causal relationship between serum TSH and BMI and obesity. The inverse variance-weighted (IVW) and MR-Egger methods were used to combine the estimation for each single-nucleotide variation (formerly single-nucleotide polymorphism). Based on the preliminary MR results, free thyroxine (fT4) and free 3,5,3'-triiodothyronine (fT3) levels were also set as outcomes to further analyze the impact of BMI on them. BMI and obesity were treated as the outcomes to evaluate the effect of serum TSH on them, and TSH was set as the outcome to estimate the effect of BMI and obesity on it.
IVW and MR-Egger results both indicated that genetically driven serum TSH did not causally lead to changes in BMI or obesity. Moreover, the IVW method showed that the TSH level could be significantly elevated by genetically predicted high BMI (β = .038, SE = 0.013, P = .004). In further MR analysis, the IVW method indicated that BMI could causally increase the fT3 (β = 10.123, SE = 2.523, P < .001) while not significantly affecting the fT4 level.
Together with fT3, TSH can be significantly elevated by an increase in genetically driven BMI.
此前已有多项流行病学研究探讨了血清促甲状腺激素（TSH）与肥胖特征之间的关联，但两者之间的因果关系尚未确定。
本研究旨在确定和分析血清 TSH 水平与肥胖相关特征（体重指数[BMI]和肥胖）之间的因果关系。
检索了最新的 TSH、BMI 和肥胖全基因组关联研究（GWAS），以获取完整的统计数据。采用双向 2 样本孟德尔随机化（MR）分析来探讨血清 TSH 与 BMI 和肥胖之间的因果关系。采用逆方差加权（IVW）和 MR-Egger 方法结合每个单核苷酸变异（之前称为单核苷酸多态性）的估计值。基于初步的 MR 结果，还将游离甲状腺素（fT4）和游离 3,5,3'-三碘甲状腺原氨酸（fT3）水平作为结局进一步分析 BMI 对它们的影响。将 BMI 和肥胖作为结局来评估血清 TSH 对它们的影响，将 TSH 作为结局来估计 BMI 和肥胖对其的影响。
IVW 和 MR-Egger 结果均表明，遗传驱动的血清 TSH 不会导致 BMI 或肥胖发生变化。此外，IVW 方法显示，遗传预测的高 BMI 可显著升高 TSH 水平（β=0.038，SE=0.013，P=0.004）。在进一步的 MR 分析中，IVW 方法表明 BMI 可以引起 fT3 显著升高（β=10.123，SE=2.523，P<0.001），但对 fT4 水平没有显著影响。
与 fT3 一起，TSH 可因遗传驱动的 BMI 增加而显著升高。
