Zhang Xinghao, Wu Pengfei, Chen Yuyao, Zhang Wan, Xia Kun, Hu Huiyu, Zhou Ping
Department of Ultrasound, Third Xiangya Hospital, Central South University, Changsha, China.
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Front Endocrinol (Lausanne). 2020 Nov 12;11:601956. doi: 10.3389/fendo.2020.601956. eCollection 2020.
The association between normal range thyroid function and offspring birth weight has been postulated, but evidence from observational studies is prone to be confounded. We conducted a two-sample Mendelian randomization (MR) study to explore the causal effects of maternal thyroid stimulating hormone (TSH) and free thyroxine (FT4) on birth weight.
We utilized public shared summary-level statistics from European-ancestry genome wide association studies. We obtained 40 and 21 single nucleotide polymorphisms as instrumental variables, which were associated with TSH and FT4 levels at genome-wide significance ( < 5 × 10). Partitioned maternal effects on birth weight were retrieved from datasets contributed by the Early Growth Genetics Consortium. Inverse-variance weighted method was employed in the primary MR analysis and multiple sensitivity analyses were implemented.
Genetically determined normal range thyroid function was not causally associated with offspring birth weight. Each one standard deviation (SD) increase in maternal TSH was associated with 0.002 SD higher of birth weight (95% confidence interval [CI], -0.021 to 0.025; = 0.87). Similarly, change in birth weight was -0.001 SD (95% CI, -0.031 to 0.029; = 0.94) per one SD higher in maternal FT4. Consistent results were yielded additional MR methods. Sensitivity analyses demonstrated no presence of horizontal pleiotropy or heterogeneity.
This MR study did not identify a causality between normal range thyroid function and offspring birth weight in the Europeans.
甲状腺功能正常范围与后代出生体重之间的关联已被提出，但观察性研究的证据容易受到混杂因素的影响。我们进行了一项两样本孟德尔随机化（MR）研究，以探讨母亲促甲状腺激素（TSH）和游离甲状腺素（FT4）对出生体重的因果影响。
我们利用了欧洲血统全基因组关联研究的公开共享汇总统计数据。我们获得了40个和21个单核苷酸多态性作为工具变量，它们在全基因组水平上与TSH和FT4水平相关（<5×10）。从早期生长遗传学联盟提供的数据集中检索出母亲对出生体重的分区效应。主要的MR分析采用逆方差加权法，并进行了多次敏感性分析。
遗传决定的正常范围甲状腺功能与后代出生体重无因果关系。母亲TSH每增加一个标准差（SD），出生体重就会高出0.002 SD（95%置信区间[CI]，-0.021至0.025；P = 0.87）。同样，母亲FT4每升高一个标准差，出生体重的变化为-0.001 SD（95% CI，-0.031至0.029；P = 0.94）。其他MR方法也得出了一致的结果。敏感性分析表明不存在水平多效性或异质性。
这项MR研究未发现欧洲人中正常范围甲状腺功能与后代出生体重之间存在因果关系。
