月经初潮年龄与特发性肺纤维化：两样本孟德尔随机研究。

Age at menarche and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study.

机构信息

Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.

Department of Neurology, Third Affiliated Hospital of Soochow University, Changzhou, 213003, Jiangsu, China.

出版信息

BMC Pulm Med. 2024 Mar 6;24(1):117. doi: 10.1186/s12890-024-02936-8.

DOI:10.1186/s12890-024-02936-8

PMID:38448907

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10916238/

Abstract

BACKGROUND

Sex difference in the incidence rate of idiopathic pulmonary fibrosis (IPF) indicates that estrogen has a certain protective effect on the disease. Nevertheless, there is a dearth of study investigating the association between factors pertaining to endogenous estrogen exposure level, such as age at menarche (AAM) in women, and IPF. Our study intended to employ Mendelian randomization (MR) method to elucidate the causal association between AAM and IPF.

METHODS

Our study utilized AAM as a measure of endogenous estrogen exposure and investigated its causal effect on the risk of IPF through MR. We employed the inverse variance weighted (IVW) method to assess the causal relationship between AAM and IPF risk, with supplementary analyses conducted using the weighted median estimator (WME) and MR-Egger method. Several sensitivity analyses were performed to assess the dependability of MR estimates.

RESULTS

A total of 9 selected single nucleotide polymorphisms (SNPs) significantly associated with AAM were selected as instrumental variables. The IVW method showed that genetically later AAM was associated with an increased risk of IPF (odds ratio [OR] = 1.0014, 95%confidence interval [CI] = 1.0005-1.0023, p = 0.001). The median weighting method and the MR-Egger method obtained similar estimates, and no heterogeneity or pleiotropy was found, indicating that the results were robust.

CONCLUSIONS

Our MR study suggested a causal relationship between a later onset of menarche and a heightened susceptibility to IPF.

摘要

背景

特发性肺纤维化（IPF）发病率的性别差异表明雌激素对该疾病有一定的保护作用。然而，目前缺乏研究调查与内源性雌激素暴露水平相关的因素（如女性初潮年龄（AAM））与 IPF 之间的关系。我们的研究旨在采用孟德尔随机化（MR）方法阐明 AAM 与 IPF 之间的因果关系。

方法

我们的研究将 AAM 作为内源性雌激素暴露的衡量标准，并通过 MR 研究其对 IPF 风险的因果影响。我们采用逆方差加权（IVW）方法评估 AAM 与 IPF 风险之间的因果关系，并使用加权中位数估计量（WME）和 MR-Egger 方法进行补充分析。进行了几项敏感性分析，以评估 MR 估计的可靠性。

结果

共选择了 9 个与 AAM 显著相关的单核苷酸多态性（SNP）作为工具变量。IVW 方法表明，遗传上较晚的 AAM 与 IPF 风险增加相关（优势比 [OR] = 1.0014，95%置信区间 [CI] = 1.0005-1.0023，p = 0.001）。中位数加权法和 MR-Egger 法得到了相似的估计值，且未发现异质性或多效性，表明结果稳健。