■越来越多的观察性研究表明,激素生殖因素与卵巢囊肿有关,一种常见的妇科疾病。通过调查生殖因素的因果关系,包括第一胎年龄(AFB),进行了两个样本的孟德尔随机化(MR)。自然绝经年龄(ANM),和初潮年龄(AAM),和卵巢囊肿(OC)的风险。
■摘要统计是从大型全基因组关联研究(GWAS)收集的,我们使用了两个样本的MR研究来阐明AFB暴露之间的因果关系(N=542,901),ANM(N=69,360),和AAM(N=29,346)和OC的结果(N病例=20,750,N对照=107,564)。我们分别选择了51、35和6个单核苷酸多态性(SNP)作为工具变量(IVs),用于测定AFB的影响。ANM,和OC上的AAM,分别。然后,因果关系通过多种方法进行了检验,包括逆方差加权法,MR-Egger回归,和加权中位数法。此外,MR-PRESSO方法也用于验证水平多效性。随后,我们调整MR设计的混杂因素。
■MR分析结果表明,AFB与OC呈负相关(IVWBeta:-0.09,OR:0.91,95%CI:0.86-0.96,p=0.00185),AAM越大,OC风险越低(IVWβ:-0.10,OR:0.91,95%CI:0.82-0.99,p=0.0376)。然而,ANM与OC呈正相关(IVWβ:0.05,OR:1.05,95%CI:1.03-1.08,p=8.38×10-6)。调整BMI后,酒精摄入频率,曾经抽烟,我们还获得了AFB和OC之间的负相关关系(p<0.005)。同时,我们调整了体重,酒精摄入频率,和高度,然后发现年龄较大的AMN与OC风险增加之间存在因果关系(p<0.005)。
■生殖因素对OC发育的因果影响,受AFB影响,ANM,和AAM,被发现令人信服。在调整了混杂因素之后,我们还成功地发现了年轻AFB的实质性因果效应,年轻的AAM,和年龄较大的ANM患OC的风险增加。
Increasing observational studies have indicated that hormonal reproductive factors were associated with ovarian cyst, a common gynecological disease. A two-sample Mendelian randomization (MR) was carried out by investigating the causality of reproductive factors including age at first birth (AFB), age at natural menopause (ANM), and age at menarche (AAM), and the risk of ovarian cyst (OC).
Summary statistics were collected from a large genome-wide association
study (GWAS), and we used a two-sample MR
study to clarify the causal association between the exposure of AFB (N = 542,901), ANM (N = 69,360), and AAM (N = 29,346) and the outcome of the OC (N case = 20,750, N control = 107,564). We separately selected 51, 35, and 6 single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for assaying the influence of AFB, ANM, and AAM on OC, respectively. Then, the causal relationship was tested through multiple approaches including an inverse-variance weighted method, an MR-Egger regression, and a weighted median method. In addition, the MR-PRESSO method was also used to verify the horizontal pleiotropy. Subsequently, we adjust the confounders for MR design.
The MR analysis results showed that AFB was negatively associated with the OC (IVW Beta: -0.09, OR: 0.91, 95% CI: 0.86-0.96, p = 0.00185), and the greater AAM decreased the risk of OC (IVW Beta: -0.10, OR: 0.91, 95% CI: 0.82-0.99, p = 0.0376). However, ANM has a positive correlation with the OC (IVW Beta: 0.05, OR: 1.05, 95% CI: 1.03-1.08, p = 8.38 × 10-6). After adjusting BMI, alcohol intake frequency, and ever smoked, we also obtained a negative relationship between AFB and OC (p < 0.005). Meanwhile, we adjusted weight, alcohol intake frequency, and height, and then found a causal relationship between older AMN and an increased risk of OC (p < 0.005).
A causal effect of reproductive factors on the development of OC, affected by AFB, ANM, and AAM, was found convincingly. After adjusting the confounders, we also successfully found the substantial causal effect of younger AFB, younger AAM, and older ANM on an increased risk of OC.