Abstract
Observational studies suggest menopause, especially at an early age, is associated with lower lung function. This association may be causal or could be explained by residual confounding (e.g. smoking). We used Mendelian randomization (MR) to assess the causal effect of age at menopause on lung function.
Using UK Biobank data of 94,742 naturally post-menopausal women (age 41-71), we performed MR analyses of the effect of age at menopause on FVC, FEV1 and FEV1/FVC, using 55 uncorrelated SNPs as instrumental variables (IVs) for age at menopause. We examined heterogeneity across IVs to assess pleiotropy. The corresponding observational associations were evaluated using linear regression adjusted for confounders.
The observational analysis showed a statistically significant increase in FEV1, FVC and FEV1/FVC per year increase in age at menopause, while the MR analysis showed a statistically significant reduction in FEV1 and FEV1/FVC, with no effect on FVC. Although there was heterogeneity suggesting pleiotropy (I2>41, p<0.0001), the results were consistent when using MR methods robust to pleiotropy (random-effect IVW, weighted median, MR Egger – See Figure).
Our preliminary MR analysis suggests that earlier menopause protects against airway obstruction, contradicting observational findings. This conclusion did not change when limiting the analysis to women who never used HRT. We are currently further investigating pleiotropy. (ALEC, EU Grant #633212)
Footnotes
Cite this article as: European Respiratory Journal 2018 52: Suppl. 62, PA1275.
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- Copyright ©the authors 2018