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

## TL;DR

Later age at menarche is linked to a higher risk of idiopathic pulmonary fibrosis, suggesting lower estrogen exposure may increase disease susceptibility.

## Contribution

This study is the first to use Mendelian randomization to establish a causal link between age at menarche and idiopathic pulmonary fibrosis.

## Key findings

- Genetically later age at menarche was associated with increased IPF risk (OR = 1.0014, p = 0.001).
- Results were consistent across multiple MR methods and showed no heterogeneity or pleiotropy.
- Findings suggest a protective role of endogenous estrogen against IPF.

## Abstract

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.

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.

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.

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