PURPOSE Adulthood and childhood obesity are both associated with reproductive diseases and gynecological cancers in females. However, the causal factors associated with these observations have yet to be identified. Mendelian randomization is a process that is independent of inverse bias and confounding and can act as a random control trial in which genetic groups are settled during meiosis, thus representing an effective tool with which to investigate causality. METHODS We carried out several Mendelian randomization trials based on the combined genetic scores of 75 adult-associated and 15 childhood-associated body mass index (BMI) single nucleotide polymorphisms (SNPs), databases for several gynecological cancers and reproductive diseases from the UK Biobank (with 194,153 participants), using the traditional inverse-variance weighted (IVW) method as the main method. RESULTS Elevated adult-associated BMI scores (odds ratio [OR] = 1.003; 95% confidence interval [CI]: 1.001-1.004) and childhood-associated BMI scores (OR = 1.003; 95% CI: 1.001-1.004) were related to a higher risk of the polycystic ovarian syndrome (PCOS), as determined by the traditional IVW method. The random IVW method further revealed a nominal negative causal association between childhood-associated BMI and subsequent endometriosis (OR = 0.995; 95% CI: 0.991-0.999). CONCLUSIONS Consistent with observational consequences, our findings indicated that adulthood obesity may play role in the development of PCOS and that childhood obesity can increase the risk of PCOS but may reduce the incidence of endometriosis in later life. Further research is now needed to validate our findings and identify the precise mechanisms involved.

中文翻译：

---

女性健康中的儿童和成人肥胖问题：孟德尔随机研究。

目的 成年期和儿童期肥胖都与女性的生殖疾病和妇科癌症有关。然而，与这些观察结果相关的因果因素尚未确定。孟德尔随机化是一个独立于逆偏倚和混杂因素的过程，可以作为随机对照试验，其中遗传组在减数分裂期间得到解决，因此代表了研究因果关系的有效工具。方法 我们基于 75 个成人相关和 15 个儿童相关体重指数 (BMI) 单核苷酸多态性 (SNP) 的综合遗传评分、来自英国生物库的几种妇科癌症和生殖疾病数据库进行了几项孟德尔随机试验。有 194,153 名参与者），采用传统的逆方差加权（IVW）方法作为主要方法。结果 升高的成人相关 BMI 评分（优势比 [OR] = 1.003；95% 置信区间 [CI]：1.001-1.004）和儿童相关 BMI 评分（OR = 1.003；95% CI：1.001-1.004）与根据传统的 IVW 方法确定的多囊卵巢综合征 (PCOS) 的风险更高。随机 IVW 方法进一步揭示了儿童期相关 BMI 与随后的子宫内膜异位症之间存在名义上的负因果关系（OR = 0.995；95% CI：0.991-0.999）。结论与观察结果一致，我们的研究结果表明，成年期肥胖可能在 PCOS 的发展中发挥作用，儿童期肥胖会增加 PCOS 的风险，但可能会降低晚年子宫内膜异位症的发病率。