medRxiv : the preprint server for health sciences · 2026

Gene-by-Sleep Duration Interaction for Glycemic Traits in over 480,000 Individuals.

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Wang Heming, Nagarajan Pavithra, Miller Clint L, Bentley Amy R, Noordam Raymond, Westerman Kenneth E, Brown Michael R, Kraja Aldi T, O'Connell Jeffrey R, Schwander Karen, Li Changwei, Sanghvi Mihir M, Song Yipei, Bartz Traci M, Braunack-Mayer Vincent, Chen Ling, Du Jiawen, Dunca Diana, Feitosa Mary F, Gudmundsdottir Valborg, Guo Xiuqing, Harris Sarah E, Highland Heather M, Huang Zhijie, Kang Changhoon, Lakka Timo A, Lefevre Christophe, Luan Jian'an, Lyytikäinen Leo-Pekka, Missikpode Celestin, Morrison John L, Palmer Nicholette D, Richmond Anne, Shahisavandi Mina, Tang Jingxian, van der Most Peter J, Weiss Stefan, Yu Chenglong, Zhu Wanying, Ansari Md Abu Yusuf, Anugu Pramod, Aschard Hugues, Ashok Kaavya, Attia John R, Bazzano Lydia A, Cade Brian E, Campbell Archie, Dimitrov Latchezar M, Do Anh, Faquih Tariq, FinesilverSmith Sandy L, Fisher-Hoch Susan P, Fretts Amanda M, Gharib Sina A, Goodarzi Mark O, Graff Mariaelisa, Gu Charles, Hanson Paul, He Jiang, Heikkinen Sami, Hixson James, Hsu Sarah, Kähönen Mika, Kho Minjung, Kim Hyunju, Komulainen Pirjo, Launer Lenore J, Lemaitre Rozenn N, Lifelines Cohort Study, McNeil John J, McCormick Joseph B, Nolte Ilja M, Raffield Laura M, Raitakari Olli T, Ramírez Julia, Riha Renata L, Risch Martin, Risch Lorenz, Russ Tom C, Sarnowski Chloé, Schram Miranda T, Scott Rodney J, Sofer Tamar, Sun Quan, Völker Uwe, Völzke Henry, Wang Yujie, van Dijk Ko Willems, Wood Alexis C, Young Kristin L, Zhang Ruiyuan, Zhu Xiaofeng, Below Jennifer E, Conen David, Cox Simon R, Fox Ervin R, Franceschini Nora, Ghanbari Mohsen, Grabe Hans Jörgen, Gudnason Vilmundur, Hayward Caroline, Holliday Elizabeth G, Jaquish Cashell E, Lacaze Paul, Lee Seunggeun, Lehtimäki Terho, Liu Ching-Ti, Morrison Alanna C, North Kari E, Peyser Patricia A, Province Michael A, Psaty Bruce M, Rauramaa Rainer, Rosendaal Frits R, Rotter Jerome I, Snieder Harold, Wagenknecht Lynne E, Wareham Nicholas J, Giri Ayush, Kelly Tanika N, Munroe Patricia B, Gauderman James, Winkler Thomas W, de Vries Paul S, Rao Dabeeru C, Manning Alisa K, Chen Han, de Las Fuentes Lisa, Redline Susan, Meigs James B

Аннотация

Both short and long sleep duration have been associated with poor glycemic control and an increased risk of developing type 2 diabetes mellitus. Although sleep duration may differentially modify the effects of genetic risk factors for type 2 diabetes, this has not been systematically investigated. In the present study, we conducted genome-wide gene by sleep duration meta-analyses, separately assessing interactions of short and long sleep, for fasting glucose, fasting insulin, and hemoglobin A1c in up to 489,309 individuals without diabetes from seven different population groups. In total, 16 loci were identified to interact with sleep duration - six with short sleep and ten with long sleep. Of these, four loci were identified through cross-population meta-analysis. Mapped genes exhibit pathway connections to pericyte apoptosis, NMDA receptor activity, the GLUT1 receptor, neurological health, and sleep architecture. Eleven loci (VRK2, PCDH7, TFAP2A, CAP2, PAPPA, ZCCHC2, MYH9, SGIP1, JAKMIP3, RRAS2, MAPT) have not been reported in previous glycemic trait genome-wide association studies. Interaction loci identify divergent biological mechanisms for short and long sleep duration influencing glycemic control, suggesting specific pathways of intervention for precision medicine approaches to diabetes prevention and management.

Gene-by-Sleep Duration Interaction for Glycemic Traits in over 480,000 Individuals.

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