Abstract
BACKGROUND: Although a connection between circadian rhythm and polycystic ovarian syndrome (PCOS) has been shown in previous studies, the exact cause of this association is not well understood. PURPOSE: This study aimed to use Mendelian randomization (MR) method to analyze the potential association between getting up in the morning and chronotype with PCOS, and a cross-sectional study was conducted to further validate these results. METHODS: Using summary information from large-scale genome-wide association studies (GWASs) in people of European ancestry, we conducted univariable MR (UVMR) and multivariable MR (MVMR) analyses to examine the causal effect of genetically determined getting up in the morning and chronotype on PCOS. We also investigated the association between wake-up time and sleep midpoint with the risk of PCOS and total testosterone (TT) levels in a cohort of 777 women of reproductive age. RESULTS: Our findings indicate a causal relationship between the genetic prediction of getting up in the morning and chronotype with a reduced incidence of PCOS. In a cross-sectional study, a sleep midpoint of > 4:00 was linked to a higher risk of PCOS and increased TT levels than a sleep midpoint of < 3:30. In women with a BMI < 24 kg/m(2), earlier wake-up times and sleep midpoints were associated with a lower risk of PCOS and decreased TT levels. CONCLUSION: This study indicates that a genetic predisposition to getting up in the morning and chronotype are linked to a reduced risk of PCOS. Additionally, earlier wake-up times and sleep midpoints are associated with a lower risk of PCOS and decreased TT levels.