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

The biological mechanisms of how sleep duration impacts type 2 diabetes pathogenesis and glycemic control are unclear.This study reveals 16 loci (11 novel) that interact with either short or long sleep duration to influence hemoglobin A1c, fasting glucose, or fasting insulin. Short and long sleep duration loci were non-overlapping.Regulation of copper and diacylglycerol levels appear as distinct cellular mechanisms implicated by long and short sleep duration loci respectively.Identified gene targets present insight for potential type 2 diabetes therapeutic design approaches related to JIP1-JNK interaction disruption, pericyte health, NMDA receptor activity, anti-inflammatory and leptin-enhancing dietary supplements, and serpins.

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Journal
medRxiv
Published
2026-03-03
DOI
https://doi.org/10.64898/2026.03.02.26346498
Primary Topic
Sleep and related disorders
Type
article
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0.00

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article

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

Sandy FinesilverSmith, H. Wang, Alexis Wood, Renata L. Riha et al.
medRxiv
Sleep and related disorders
article

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

Sandy FinesilverSmith, H. Wang, Alexis Wood, Renata L. Riha, Christophe Lefèvre, Diana Dunca, Celestin Missikpode, Timo A. Lakka, Alisa K. Manning, Lacaze Paul, Kenneth E. Westerman, Miranda T. Schram, Cashell Jacquish, Sarah Hsu, James Gauderman, Lydia Bazzano, L Leon Chen, Joseph B. McCormick, Kaavya Ashok, Changwei Li, Julia Ramírez, T. Sofer, B. Cade, Mihir M. Sanghvi, Charles C Gu, Mandy Fretts, Ruiyuan Zhang, Wanying Zhu, MINJUNG KHO, H Snieder, Aldi T. Kraja, Jiang He, Uwe Voelker, Dabeeru C Rao, Paul A. Hanson, Vincent Braunack-Mayer, Zhijie Huang, Amy R. Bentley, Lorenz Risch, Tom C. Russ, John Morrison, Anh Do, Pramod Anugu, Jiawen Du, Clint L. Miller, Sami Heikkinen, Hugues Aschard, Anne Richmond, Hans Jörgen Grabe, James B. Meigs, Yipei Song, H. Völzke, D C Conen, Ayush Giri, Ching-Ti Liu, Ervin R Fox, Mohsen Ghanbari, V Gudnason, Sina A. Gharib, Elizabeth G. Holliday, Nora Franceschini, Mina Shahisavandi, Mariaelisa Graff, Chenglong Yu, Lenore J. Launer, Lifelines Cohort Study, Peter J. van der Most, Susan Redline, Thomas W. Winkler, Seunggeun Lee, Michael A. Province, Patricia B. Munroe, Kari E. North, Patricia A. Peyser, Tanika N. Kelly, Alanna C. Morrison, Nicholas J. Wareham, Jingxian Tang, Rozenn N. Lemaitre, Rainer Rauramaa, Lisa de las Fuentes, Olli T. Raitakari, Tariq Faquih, Simon R. Cox, Mark O. Goodarzi, Leo-Pekka Lyytikäinen, Hyunju Kim, Mary F. Feitosa, Susan P. Fisher-Hoch, Latchezar M. Dimitrov, Jerome I. Rotter, John J. McNeil, Michael R. Brown, Xiaofeng Zhu, Caroline Hayward, Ilja M. Nolte, Laura M. Raffield, Changhoon Kang, James Hixson, Valborg Gudmundsdottir, Xiuqing Guo, Jennifer E. Below, Heather M. Highland, Archie Campbell, John R. Attia, Paul S. de Vries, Karen Schwander, Md Abu Yusuf Ansari, Raymond Noordam, Bruce M. Psaty, Sarah E. Harris, Frits R. Rosendaal, Mika Kähönen, Quan Sun, Martin Risch, Lynne E. Wagenknecht, Nicholette D. Palmer, Stefan Weiss, Traci M. Bartz, Rodney J. Scott, Terho Lehtimäki
article en

Abstract

The biological mechanisms of how sleep duration impacts type 2 diabetes pathogenesis and glycemic control are unclear.This study reveals 16 loci (11 novel) that interact with either short or long sleep duration to influence hemoglobin A1c, fasting glucose, or fasting insulin. Short and long sleep duration loci were non-overlapping.Regulation of copper and diacylglycerol levels appear as distinct cellular mechanisms implicated by long and short sleep duration loci respectively.Identified gene targets present insight for potential type 2 diabetes therapeutic design approaches related to JIP1-JNK interaction disruption, pericyte health, NMDA receptor activity, anti-inflammatory and leptin-enhancing dietary supplements, and serpins.

medRxiv
Broad Institute (US), Boston University (US), University of North Carolina at Chapel Hill (US), Tulane University (US), University of Southern California (US), University of Bern (CH), University of Maryland, Baltimore (US), Cedars-Sinai Medical Center (US), Brigham and Women's Hospital (US), National Institutes of Health (US), NHS Lothian (GB), University Medical Center Groningen (NL), Children's Hospital of Philadelphia (US), Harvard University (US), Seoul National University (KR), Institut Pasteur (FR), University of Iceland (IS), Queen Mary University of London (GB), Tampere University (FI), University of Groningen (NL), University of Eastern Finland (FI), University of Liechtenstein (LI), Vanderbilt University (US), University of Washington (US), Washington University in St. Louis (US), Université Paris Cité (FR), Barts Health NHS Trust (GB), University of Cambridge (GB), Universidad de Zaragoza (ES), University of Michigan (US), Universitätsmedizin Greifswald (DE), Leiden University Medical Center (NL), University Hospital of Bern (CH), UCLA Medical Center (US), German Center for Neurodegenerative Diseases (DE), Erasmus MC (NL), Turku University Hospital (FI), Edinburgh Cancer Research (GB), Population Health Research Institute (CA), Jackson Memorial Hospital (US), University of Mississippi Medical Center (US), University of Illinois Chicago (US), Massachusetts General Hospital (US), National Human Genome Research Institute (US), Alzheimer Scotland (GB), Kuopio University Hospital (FI), VA Tennessee Valley Healthcare System (US), Roche (Netherlands) (NL), Private University in the Principality of Liechtenstein (LI), Tampere University Hospital (FI), German Centre for Cardiovascular Research (DE), Tampere University (FI), Fimlab (Finland) (FI), National Institute on Aging (US), Circadian (United States) (US), Children's Nutrition Research Center at Baylor College of Medicine (US), Kantonsspital Graubünden (CH), William Harvey Research Institute (GB), Icelandic Heart Association (IS), MRC Epidemiology Unit (GB), Institute of Genetics and Cancer (GB), The University of Texas Health Science Center (US), Harbor–UCLA Medical Center (US), Wake Forest University (US), University of Virginia (US), Monash University (AU), Case Western Reserve University (US), University of Regensburg (DE), University of Newcastle Australia (AU), The University of Texas Southwestern Medical Center (US), Vanderbilt University Medical Center (US), The University of Texas Health Science Center at Houston (US), The Hague University of Applied Sciences (NL), McMaster University (CA), University of Edinburgh (GB)
U.S. Department of Health and Human Services, Amgen, Eli Lilly and Company, AstraZeneca, Servier, Neuraxpharm, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute on Minority Health and Health Disparities, Cilag
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Sleep and related disorders
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