The Key Laboratory of Reproductive Genetics (Zhejiang University), Ministry of Education, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Endocrine. 2022 Feb;75(2):400-408. doi: 10.1007/s12020-021-02867-y. Epub 2021 Sep 20.
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.
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.
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).
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.
成年期和儿童期肥胖均与女性生殖系统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。孟德尔随机化是一种独立于反向偏倚和混杂因素的过程，可以作为一种随机对照试验，其中在减数分裂过程中确定遗传群体，因此是一种有效的因果关系研究工具。
我们基于 75 个与成人相关的和 15 个与儿童相关的体重指数（BMI）单核苷酸多态性（SNP）的综合遗传评分，在英国生物银行（194153 名参与者）中进行了几项孟德尔随机化试验，使用传统的逆方差加权（IVW）方法作为主要方法，研究了几种妇科癌症和生殖系统疾病数据库。
根据传统的 IVW 方法，升高的与成人相关的 BMI 评分（比值比[OR] = 1.003；95%置信区间[CI]：1.001-1.004）和与儿童相关的 BMI 评分（OR = 1.003；95% CI：1.001-1.004）与多囊卵巢综合征（PCOS）的风险增加有关。随机 IVW 方法进一步显示，儿童时期 BMI 与随后的子宫内膜异位症（OR = 0.995；95% CI：0.991-0.999）之间存在名义上的负因果关系。
与观察结果一致，我们的研究结果表明，成年肥胖可能在 PCOS 的发生中起作用，而儿童肥胖可能会增加 PCOS 的风险，但可能会降低晚年子宫内膜异位症的发病率。现在需要进一步的研究来验证我们的发现并确定所涉及的确切机制。
