Wang Lianke, Xu Fei, Zhang Qiang, Chen Jiajun, Zhou Qianyu, Sun Changqing
Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, China.
Department of Community Nursing, College of Nursing and Health, Zhengzhou University, Henan, Zhengzhou, China.
Clin Endocrinol (Oxf). 2023 Feb;98(2):212-220. doi: 10.1111/cen.14831. Epub 2022 Oct 25.
Observational studies suggest birth weight and childhood obesity are closely associated with age at menarche. However, the relationships between them are currently inconsistent and it remains elusive whether such associations are causal. Therefore, the aim of the study was to investigate whether there existed causal relationships between birth weight, childhood obesity and age at menarche.
DESIGN, PATIENTS AND MEASUREMENTS: A two-sample Mendelian randomization (MR) study. The standard inverse variance weighted MR analyses were adopted to evaluate the causal effects of birth weight (n = 143,677), childhood body mass index (BMI) (n = 39,620) on age at menarche (n = 182,416) with summary statistics from large-scale genome-wide association studies (GWASs). Meanwhile, we validated our MR results with some sensitivity analyses including maximum likelihood, weighted-median and MR pleiotropy residual sum and outlier methods.
The present study showed that each one standard deviation (1-SD) lower birth weight was predicted to result in a 0.1479 years earlier of age at menarche (β = .1479, 95% confidence interval [CI] = 0.0422-0.2535; p = 0.0061). We also found that genetically predicted 1-SD increase in childhood BMI was causally associated with early age at menarche (β = -.3966, 95% CI = -0.5294 to -0.2639; p = 4.73E-09).
Our MR study suggests the causal effect of lower birth weight and higher childhood BMI on the increased risk of earlier menarche. It may be the opportune time to carry out weight control intervention in prenatal and early childhood development periods to prevent early menarche onset, thus decreasing the future adverse consequences.
观察性研究表明出生体重和儿童期肥胖与初潮年龄密切相关。然而，它们之间的关系目前并不一致，这种关联是否具有因果关系仍不明确。因此，本研究的目的是调查出生体重、儿童期肥胖与初潮年龄之间是否存在因果关系。
设计、研究对象与测量方法：一项两样本孟德尔随机化（MR）研究。采用标准的逆方差加权MR分析，利用大规模全基因组关联研究（GWAS）的汇总统计数据，评估出生体重（n = 143,677）、儿童期体重指数（BMI）（n = 39,620）对初潮年龄（n = 182,416）的因果效应。同时，我们通过一些敏感性分析验证了我们的MR结果，包括最大似然法、加权中位数法以及MR多效性残差和离群值法。
本研究表明，出生体重每降低一个标准差（1-SD），预计初潮年龄会提前0.1479岁（β = 0.1479，95%置信区间[CI] = 0.0422 - 0.2535；p = 0.0061）。我们还发现，基因预测的儿童期BMI每增加1-SD与初潮年龄提前存在因果关联（β = -0.3966，95% CI = -0.5294至-0.2639；p = 4.73×10⁻⁹）。
我们的MR研究表明，较低的出生体重和较高的儿童期BMI对初潮提前风险增加具有因果效应。在产前和儿童早期发育阶段进行体重控制干预，以预防初潮过早开始，从而减少未来的不良后果，可能是合适的时机。
