Polycystic ovary syndrome and lung function: a Mendelian randomization study

Polycystic ovary syndrome (PCOS) affects between 5-20% of women. Oligomenorrhea (long and/or irregular cycles) is a common PCOS symptom and has been associated with lower forced vital capacity (FVC). We aimed to estimate the effect of PCOS on lung function using Mendelian randomization (MR), an approach that uses genetic variants as proxies to overcome confounding and reverse causation. We used an inverse variance-weighted (IVW) MR method to estimate the causal effect of PCOS on spirometric restriction (FVC The MR estimate shows that PCOS is associated with a 10% higher risk of spirometric restriction (OR 1.10 [1.05 to 1.15]), with no indication of pleiotropy (Q test P= 0.86; I2= 0). Estimates were similar when using MR methods adjusting for pleiotropy and when limiting the analysis to non-asthmatics (OR 1.12 [1.06 to 1.18]) or SNPs significant in European women (OR 1.10 [1.04 to 1.16]). Effect estimates were similar in normal weight and overweight (>26 kg/m2) women (interaction P=0.89). There was no association between PCOS and airflow obstruction (OR 0.98 [0.94 to 1.02]). Our MR results suggest that PCOS increases the risk of spirometric restriction. Further studies are needed to investigate the possible underlying mechanism. (ALEC, EU Grant #633212)