Getting Up in the Morning and Chronotype in Relation to Polycystic Ovarian Syndrome: A Mendelian Randomization and Cross-Sectional Study

Diliqingna Dilimulati,1,* Jiayi Lu,2,* Jinghua Li,2,* Meili Cai,1 Yuqin Zhang,1 Xiaowen Shao,3 Haibing Chen,1 Qian Wan,4 Fang He,4 Chaoyan Yue,5 Manna Zhang,1,6 Shen Qu1 1Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2Department of Clinical Laboratory, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 3Department of Obstetrics and Gynecology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 4Department of Endocrinology and Metabolism, The First People’s Hospital of Chenzhou, Chenzhou, Hunan, 423000, People’s Republic of China; 5Department of Laboratory Medicine, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, People’s Republic of China; 6Department of General Practice, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China*These authors contributed equally to this workCorrespondence: Manna Zhang, Department of Endocrinology and Metabolism, Shanghai Tenth People’s Hospital, No. 301, Middle Yanchang Road, Jingan District, Shanghai, 200072, People’s Republic of China, Tel +86 13774448495, Email [email protected] Chaoyan Yue, Department of Laboratory Medicine, Obstetrics and Gynecology Hospital of Fudan University, No. 419, Fangxie Road, Huangpu District, Shanghai, 200011, People’s Republic of China, Tel +86 02133189900, Email [email protected]: 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/m2, 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.Keywords: polycystic ovarian syndrome, getting up in the morning, chronotype, Mendelian randomization