A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

Pavithra Nagarajan^#¹, Thomas W Winkler^#², Amy R Bentley^#³, Clint L Miller^#^{4

5}, Aldi T Kraja^#⁶, Karen Schwander^#⁷, Songmi Lee⁸, Wenyi Wang⁹, Michael R Brown¹⁰, John L Morrison¹¹, Ayush Giri^{12

13}, Jeffrey R O'Connell¹⁴, Traci M Bartz^{15

16}, Lisa de Las Fuentes^{17

18}, Valborg Gudmundsdottir^{19

20}, Xiuqing Guo²¹, Sarah E Harris²², Zhijie Huang²³, Mart Kals²⁴, Minjung Kho²⁵, Christophe Lefevre²⁶, Jian'an Luan²⁷, Leo-Pekka Lyytikäinen^{28

29}, Massimo Mangino^{30

31}, Yuri Milaneschi^{32

33}, Nicholette D Palmer³⁴, Varun Rao³⁵, Rainer Rauramaa³⁶, Botong Shen³⁷, Stefan Stadler³⁸, Quan Sun³⁹, Jingxian Tang⁴⁰, Sébastien Thériault⁴¹, Adriaan van der Graaf⁴², Peter J van der Most⁴³, Yujie Wang⁴⁴, Stefan Weiss^{45

46}, Kenneth E Westerman^{47

48}, Qian Yang^{49

50}, Tabara Yasuharu^{51

52}, Wei Zhao^{53

54}, Wanying Zhu⁵⁵, Drew Altschul^{22

56}, Md Abu Yusuf Ansari⁵⁷, Pramod Anugu⁵⁸, Anna D Argoty-Pantoja⁴³, Michael Arzt³⁸, Hugues Aschard^{59

60}, John R Attia⁶¹, Lydia Bazzanno²³, Max A Breyer⁵⁵, Jennifer A Brody¹⁵, Brian E Cade^{1

47}, Hung-Hsin Chen⁵⁵, Yii-Der Ida Chen²¹, Zekai Chen⁴³, Paul S de Vries¹⁰, Latchezar M Dimitrov³⁴, Anh Do¹⁸, Jiawen Du³⁹, Charles T Dupont⁶², Todd L Edwards^{13

63}, Michele K Evans³⁷, Tariq Faquih^{1

47}, Stephan B Felix^{46

64}, Susan P Fisher-Hoch⁶⁵, James S Floyd^{15

66}, Mariaelisa Graff⁴⁴, Charles Gu¹⁸, Dongfeng Gu⁶⁷, Kristen G Hairston⁶⁸, Anthony J Hanley⁶⁹, Iris M Heid², Sami Heikkinen⁷⁰, Heather M Highland⁴⁴, Michelle M Hood⁵⁴, Mika Kähönen⁷¹, Carrie A Karvonen-Gutierrez⁵⁴, Takahisa Kawaguchi⁵², Setoh Kazuya⁵¹, Tanika N Kelly³⁵, Pirjo Komulainen³⁶, Daniel Levy^{72

73}, Henry J Lin²¹, Peter Y Liu²¹, Pedro Marques-Vidal^{74

75}, Joseph B McCormick⁶⁵, Hao Mei⁵⁷, James B Meigs^{47

76}, Cristina Menni³⁰, Kisung Nam²⁵, Ilja M Nolte⁴³, Natasha L Pacheco³⁷, Lauren E Petty⁵⁵, Hannah G Polikowsky⁵⁵, Michael A Province⁷, Bruce M Psaty^{15

66}, Laura M Raffield⁷⁷, Olli T Raitakari^{78

79

80}, Stephen S Rich⁸¹, Renata L Riha⁸², Lorenz Risch^{83

84}, Martin Risch^{85

86}, Edward A Ruiz-Narvaez⁸⁷, Rodney J Scott⁸⁸, Colleen M Sitlani¹⁵, Jennifer A Smith^{53

54}, Tamar Sofer^{1

89}, Maris Teder-Laving²⁴, Uwe Völker^{45

46}, Peter Vollenweider^{74

75}, Guanchao Wang⁶², Ko Willems van Dijk^{9

90}, Otis D Wilson^{13

91}, Rui Xia⁸, Jie Yao²¹, Kristin L Young⁴⁴, Ruiyuan Zhang⁹², Xiaofeng Zhu⁹³, Jennifer E Below⁵⁵, Carsten A Böger^{94

95

96}, David Conen⁹⁷, Simon R Cox²², Marcus Dörr^{46

64}, Mary F Feitosa⁷, Ervin R Fox⁹⁸, Nora Franceschini⁴⁴, Sina A Gharib⁹⁹, Vilmundur Gudnason^{19

20}, Sioban D Harlow⁵⁴, Jiang He⁹², Elizabeth G Holliday⁶¹, Zoltan Kutalik^{42

100}, Timo A Lakka^{70

101

102}, Deborah A Lawlor^{49

50}, Seunggeun Lee²⁵, Terho Lehtimäki^{28

29}, Changwei Li⁹², Ching-Ti Liu⁴⁰, Reedik Mägi²⁴, Fumihiko Matsuda⁵², Alanna C Morrison¹⁰, Brenda Wjh Penninx^{32

33}, Patricia A Peyser⁵⁴, Jerome I Rotter²¹, Harold Snieder⁴³, Tim D Spector³⁰, Lynne E Wagenknecht¹⁰³, Nicholas J Wareham²⁷, Alan B Zonderman³⁷, Kari E North⁴⁴, Myriam Fornage^{8

10}; Million Veteran Program; Adriana M Hung^{13

93}, Alisa K Manning^{104

105}, James Gauderman¹¹, Han Chen¹⁰, Patricia B Munroe¹⁰⁶, Dabeeru C Rao¹⁸, Diana van Heemst¹⁰⁷, Susan Redline^{1

47}, Raymond Noordam¹⁰⁷, Heming Wang^{108

109}

Collaborators, Affiliations

Collaborators

Million Veteran Program:
Sumitra Muralidhar, Jennifer Moser, Jennifer E Deen, Philip S Tsao, J Michael Gaziano, Elizabeth Hauser, Amy Kilbourne, Michael Matheny, Dave Oslin, Lori Churby, Stacey B Whitbourne, Jessica V Brewer, Shahpoor Alex Shayan, Luis E Selva, Saiju Pyarajan, Kelly Cho, Scott L DuVall, Mary T Brophy, Brady Stephens, Todd Connor, Dean P Argyres, Themistocles L Assimes, Adriana Hung, Henry Kranzler, Samuel Aguayo, Sunil Ahuja, Kathrina Alexander, Xiao M Androulakis, Prakash Balasubramanian, Zuhair Ballas, Elizabeth S Bast, Jean Beckham, Sujata Bhushan, Edward Boyko, David Cohen, Louis Dellitalia, Gerald Wayne Dryden Jr, L Christine Faulk, Joseph Fayad, Daryl Fujii, Saib Gappy, Frank Gesek, Jennifer Greco, Michael Godschalk, Todd W Gress, Samir Gupta, Salvador Gutierrez, John Harley, Mark Hamner, Daniel J Hogan, Robin Hurley, Pran Iruvanti, Frank Jacono, Darshana Jhala, Scott Kinlay, Michael Landry, Peter Liang, Suthat Liangpunsakul, Jack Lichy, Tze Shien Lo, C Scott Mahan, Ronnie Marrache, Stephen Mastorides, Kristin Mattocks, Paul Meyer, Jonathan Moorman, Providencia Morales, Timothy Morgan, Maureen Murdoch, Eknath Naik, James Norton, Olaoluwa Okusaga, Michael K Ong, Kris Ann Oursler, Ismene Petrakis, Samuel Poon, Emily Potter, Michael Rauchman, Amneet S Rai, Richard Servatius, Satish Sharma, River Smith, Peruvemba Sriram, Patrick Strollo Jr, Neeraj Tandon, Gerardo Villareal, Jessica Walsh, John Wells, Jeffrey Whittle, Mary Whooley, Peter Wilson, Junzhe Xu, Shing Shing Yeh, Andrew W Yen

Affiliations

¹ Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
² Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
³ Center for Research on Genomics and Global Health, National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD, USA.
⁴ Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
⁵ Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
⁶ University of Mississippi Medical Center, Jackson, MS, USA.
⁷ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.
⁹ Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
¹⁰ Human Genetics Center, Department of Epidemiology, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, USA.
¹¹ Division of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
¹² Division of Quantitative and Clinical Sciences, Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹³ Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626), Department of Veterans Affairs, Nashville, TN, USA.
¹⁴ Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁷ Cardiovascular Division, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹⁸ Center for Biostatistics and Data Science, Institute for Informatics, Data Science, and Biostatistics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹⁹ Icelandic Heart Association, Kopavogur, Iceland.
²⁰ Faculty of Medicine, Department of Health Sciences, University of Iceland, Reykjavik, Iceland.
²¹ The Institute for Translational Genomics and Population Sciences, Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
²² Department of Psychology, The University of Edinburgh, Edinburgh, UK.
²³ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
²⁴ Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
²⁵ Graduate School of Data Science, Seoul National University, Seoul, South Korea.
²⁶ Department of Data Sciences, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
²⁷ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
²⁸ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
²⁹ Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere, Finland.
³⁰ Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
³¹ National Heart & Lung Institute, Cardiovascular Genomics and Precision Medicine, Imperial College London, London, UK.
³² Department of Psychiatry, Amsterdam UMC/Vrije universiteit, Amsterdam, Netherlands.
³³ GGZ inGeest, Amsterdam, Netherlands.
³⁴ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³⁵ Division of Nephrology, Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.
³⁶ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
³⁷ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
³⁸ Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
³⁹ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁰ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴¹ Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, QC, Canada.
⁴² Statistical Genetics Group, Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
⁴³ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
⁴⁴ Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁵ Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
⁴⁶ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
⁴⁷ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁴⁸ Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA.
⁴⁹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁵⁰ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁵¹ Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
⁵² Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁵³ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
⁵⁴ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁵⁵ Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁶ School of Psychology, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁵⁷ Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁸ Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁹ Department of Computational Biology, F-75015 Paris, France Institut Pasteur, Université Paris Cité, Paris, France.
⁶⁰ Department of Epidemiology, Harvard TH School of Public Health, Boston, MA, USA.
⁶¹ School of Medicine and Public Health, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia.
⁶² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶³ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶⁴ Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
⁶⁵ School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Brownsville, TX, USA.
⁶⁶ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁶⁷ Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China.
⁶⁸ Department of Endocrinology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁶⁹ Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
⁷⁰ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
⁷¹ Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere, Finland.
⁷² Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁷³ Framingham Heart Study, Framingham, MA, USA.
⁷⁴ Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁷⁵ Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁷⁶ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁷⁷ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁷⁸ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁷⁹ Research Centre of Applied and Preventive Cardiovascular Medicine, and Department of Clinical Physiology and Nuclear Medicine, University of Turku, and Turku University Hospital, Turku, Finland.
⁸⁰ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁸¹ Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
⁸² Department of Sleep Medicine, The University of Edinburgh, Edinburgh, UK.
⁸³ Faculty of Medical Sciences, Institute for Laboratory Medicine, Private University in the Principality of Liechtenstein, Vaduz, Liechtenstein.
⁸⁴ Center of Laboratory Medicine, Institute of Clinical Chemistry, University of Bern and Inselspital, Bern, Switzerland.
⁸⁵ Central Laboratory, Cantonal Hospital Graubünden, Chur, Switzerland.
⁸⁶ Medical Laboratory, Dr. Risch Anstalt, Vaduz, Liechtenstein.
⁸⁷ Department of Nutritional Sciences, University of Michigan, Ann Arbor, MI, USA.
⁸⁸ School of Biomedical Sciences and Pharmacy, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia.
⁸⁹ CardioVascular Institute (CVI), Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁹⁰ Department of Internal Medicine, Division of Endocrinology, Leiden, Netherlands.
⁹¹ Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁹² Department of Epidemiology, O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹³ Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁹⁴ Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
⁹⁵ Department of Nephrology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany.
⁹⁶ KfH Kidney Centre Traunstein, Traunstein, Germany.
⁹⁷ Population Health Research Institute, Medicine, McMaster University, Hamilton, ON, Canada.
⁹⁸ Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁹⁹ Pulmonary, Critical Care and Sleep Medicine, Medicine, University of Washington, Seattle, WA, USA.
¹⁰⁰ Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
¹⁰¹ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁰² Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
¹⁰³ Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁰⁴ Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁰⁵ Metabolism Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰⁶ Clinical Pharmacology and Precision Medicine, Queen Mary University of London, London, UK.
¹⁰⁷ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
¹⁰⁸ Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. hwang@bwh.harvard.edu.
¹⁰⁹ Department of Medicine, Harvard Medical School, Boston, MA, USA. hwang@bwh.harvard.edu.

^# Contributed equally.

PMID: 40181193
DOI: 10.1038/s41380-025-02954-w

A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

Pavithra Nagarajan et al. Mol Psychiatry. 2025 Aug.

. 2025 Aug;30(8):3660-3672.

doi: 10.1038/s41380-025-02954-w. Epub 2025 Apr 4.

Authors

Collaborators

Million Veteran Program:
Sumitra Muralidhar, Jennifer Moser, Jennifer E Deen, Philip S Tsao, J Michael Gaziano, Elizabeth Hauser, Amy Kilbourne, Michael Matheny, Dave Oslin, Lori Churby, Stacey B Whitbourne, Jessica V Brewer, Shahpoor Alex Shayan, Luis E Selva, Saiju Pyarajan, Kelly Cho, Scott L DuVall, Mary T Brophy, Brady Stephens, Todd Connor, Dean P Argyres, Themistocles L Assimes, Adriana Hung, Henry Kranzler, Samuel Aguayo, Sunil Ahuja, Kathrina Alexander, Xiao M Androulakis, Prakash Balasubramanian, Zuhair Ballas, Elizabeth S Bast, Jean Beckham, Sujata Bhushan, Edward Boyko, David Cohen, Louis Dellitalia, Gerald Wayne Dryden Jr, L Christine Faulk, Joseph Fayad, Daryl Fujii, Saib Gappy, Frank Gesek, Jennifer Greco, Michael Godschalk, Todd W Gress, Samir Gupta, Salvador Gutierrez, John Harley, Mark Hamner, Daniel J Hogan, Robin Hurley, Pran Iruvanti, Frank Jacono, Darshana Jhala, Scott Kinlay, Michael Landry, Peter Liang, Suthat Liangpunsakul, Jack Lichy, Tze Shien Lo, C Scott Mahan, Ronnie Marrache, Stephen Mastorides, Kristin Mattocks, Paul Meyer, Jonathan Moorman, Providencia Morales, Timothy Morgan, Maureen Murdoch, Eknath Naik, James Norton, Olaoluwa Okusaga, Michael K Ong, Kris Ann Oursler, Ismene Petrakis, Samuel Poon, Emily Potter, Michael Rauchman, Amneet S Rai, Richard Servatius, Satish Sharma, River Smith, Peruvemba Sriram, Patrick Strollo Jr, Neeraj Tandon, Gerardo Villareal, Jessica Walsh, John Wells, Jeffrey Whittle, Mary Whooley, Peter Wilson, Junzhe Xu, Shing Shing Yeh, Andrew W Yen

Affiliations

¹ Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
² Department of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
³ Center for Research on Genomics and Global Health, National Human Genome Research Institute, US National Institutes of Health, Bethesda, MD, USA.
⁴ Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA.
⁵ Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
⁶ University of Mississippi Medical Center, Jackson, MS, USA.
⁷ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, USA.
⁸ Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.
⁹ Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands.
¹⁰ Human Genetics Center, Department of Epidemiology, University of Texas Health Science Center at Houston School of Public Health, Houston, TX, USA.
¹¹ Division of Biostatistics, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
¹² Division of Quantitative and Clinical Sciences, Department of Obstetrics & Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹³ Biomedical Laboratory Research and Development, Tennessee Valley Healthcare System (626), Department of Veterans Affairs, Nashville, TN, USA.
¹⁴ Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
¹⁵ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
¹⁶ Department of Biostatistics, University of Washington, Seattle, WA, USA.
¹⁷ Cardiovascular Division, Department of Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹⁸ Center for Biostatistics and Data Science, Institute for Informatics, Data Science, and Biostatistics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹⁹ Icelandic Heart Association, Kopavogur, Iceland.
²⁰ Faculty of Medicine, Department of Health Sciences, University of Iceland, Reykjavik, Iceland.
²¹ The Institute for Translational Genomics and Population Sciences, Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
²² Department of Psychology, The University of Edinburgh, Edinburgh, UK.
²³ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
²⁴ Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, Estonia.
²⁵ Graduate School of Data Science, Seoul National University, Seoul, South Korea.
²⁶ Department of Data Sciences, Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
²⁷ MRC Epidemiology Unit, University of Cambridge, Cambridge, UK.
²⁸ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
²⁹ Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere, Finland.
³⁰ Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
³¹ National Heart & Lung Institute, Cardiovascular Genomics and Precision Medicine, Imperial College London, London, UK.
³² Department of Psychiatry, Amsterdam UMC/Vrije universiteit, Amsterdam, Netherlands.
³³ GGZ inGeest, Amsterdam, Netherlands.
³⁴ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
³⁵ Division of Nephrology, Department of Medicine, University of Illinois Chicago, Chicago, IL, USA.
³⁶ Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
³⁷ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
³⁸ Department of Internal Medicine II, University Hospital Regensburg, Regensburg, Germany.
³⁹ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁰ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
⁴¹ Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec City, QC, Canada.
⁴² Statistical Genetics Group, Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
⁴³ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
⁴⁴ Department of Epidemiology, UNC Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁵ Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
⁴⁶ DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany.
⁴⁷ Department of Medicine, Harvard Medical School, Boston, MA, USA.
⁴⁸ Clinical and Translational Epidemiology Unit, Mongan Institute, Massachusetts General Hospital, Boston, MA, USA.
⁴⁹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
⁵⁰ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
⁵¹ Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan.
⁵² Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
⁵³ Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA.
⁵⁴ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
⁵⁵ Division of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁵⁶ School of Psychology, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
⁵⁷ Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁸ Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁹ Department of Computational Biology, F-75015 Paris, France Institut Pasteur, Université Paris Cité, Paris, France.
⁶⁰ Department of Epidemiology, Harvard TH School of Public Health, Boston, MA, USA.
⁶¹ School of Medicine and Public Health, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia.
⁶² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶³ Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶⁴ Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
⁶⁵ School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Brownsville, TX, USA.
⁶⁶ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁶⁷ Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science and Technology, Shenzhen, China.
⁶⁸ Department of Endocrinology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁶⁹ Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
⁷⁰ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.
⁷¹ Department of Clinical Physiology, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere, Finland.
⁷² Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁷³ Framingham Heart Study, Framingham, MA, USA.
⁷⁴ Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁷⁵ Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁷⁶ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁷⁷ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁷⁸ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁷⁹ Research Centre of Applied and Preventive Cardiovascular Medicine, and Department of Clinical Physiology and Nuclear Medicine, University of Turku, and Turku University Hospital, Turku, Finland.
⁸⁰ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁸¹ Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA.
⁸² Department of Sleep Medicine, The University of Edinburgh, Edinburgh, UK.
⁸³ Faculty of Medical Sciences, Institute for Laboratory Medicine, Private University in the Principality of Liechtenstein, Vaduz, Liechtenstein.
⁸⁴ Center of Laboratory Medicine, Institute of Clinical Chemistry, University of Bern and Inselspital, Bern, Switzerland.
⁸⁵ Central Laboratory, Cantonal Hospital Graubünden, Chur, Switzerland.
⁸⁶ Medical Laboratory, Dr. Risch Anstalt, Vaduz, Liechtenstein.
⁸⁷ Department of Nutritional Sciences, University of Michigan, Ann Arbor, MI, USA.
⁸⁸ School of Biomedical Sciences and Pharmacy, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia.
⁸⁹ CardioVascular Institute (CVI), Beth Israel Deaconess Medical Center, Boston, MA, USA.
⁹⁰ Department of Internal Medicine, Division of Endocrinology, Leiden, Netherlands.
⁹¹ Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
⁹² Department of Epidemiology, O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹³ Department of Population and Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁹⁴ Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
⁹⁵ Department of Nephrology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany.
⁹⁶ KfH Kidney Centre Traunstein, Traunstein, Germany.
⁹⁷ Population Health Research Institute, Medicine, McMaster University, Hamilton, ON, Canada.
⁹⁸ Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁹⁹ Pulmonary, Critical Care and Sleep Medicine, Medicine, University of Washington, Seattle, WA, USA.
¹⁰⁰ Center for Primary Care and Public Health, University of Lausanne, Lausanne, Switzerland.
¹⁰¹ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland.
¹⁰² Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
¹⁰³ Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁰⁴ Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁰⁵ Metabolism Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰⁶ Clinical Pharmacology and Precision Medicine, Queen Mary University of London, London, UK.
¹⁰⁷ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, Netherlands.
¹⁰⁸ Division of Sleep and Circadian Disorders, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. hwang@bwh.harvard.edu.
¹⁰⁹ Department of Medicine, Harvard Medical School, Boston, MA, USA. hwang@bwh.harvard.edu.

^# Contributed equally.

PMID: 40181193
DOI: 10.1038/s41380-025-02954-w

Abstract

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discovered 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management.

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Conflict of interest statement

Competing interests: CLM has received funding from AstraZeneca not related to the current study. BMP serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. DC receives consultancy fees from Roche Diagnostics and Trimedics and speaker fees from Servier. DAL has received support from Medtronic LTD and Roche Diagnostics for biomarker research not related to the current study. HC receives consulting fees from Character Biosciences. The remaining authors declare no competing interests.

Update of

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.
Nagarajan P, Winkler TW, Bentley AR, Miller CL, Kraja AT, Schwander K, Lee S, Wang W, Brown MR, Morrison JL, Giri A, O'Connell JR, Bartz TM, de Las Fuentes L, Gudmundsdottir V, Guo X, Harris SE, Huang Z, Kals M, Kho M, Lefevre C, Luan J, Lyytikäinen LP, Mangino M, Milaneschi Y, Palmer ND, Rao V, Rauramaa R, Shen B, Stadler S, Sun Q, Tang J, Thériault S, van der Graaf A, van der Most PJ, Wang Y, Weiss S, Westerman KE, Yang Q, Yasuharu T, Zhao W, Zhu W, Altschul D, Ansari MAY, Anugu P, Argoty-Pantoja AD, Arzt M, Aschard H, Attia JR, Bazzanno L, Breyer MA, Brody JA, Cade BE, Chen HH, Ida Chen YD, Chen Z, de Vries PS, Dimitrov LM, Do A, Du J, Dupont CT, Edwards TL, Evans MK, Faquih T, Felix SB, Fisher-Hoch SP, Floyd JS, Graff M, Gu C, Gu D, Hairston KG, Hanley AJ, Heid IM, Heikkinen S, Highland HM, Hood MM, Kähönen M, Karvonen-Gutierrez CA, Kawaguchi T, Kazuya S, Kelly TN, Komulainen P, Levy D, Lin HJ, Liu PY, Marques-Vidal P, McCormick JB, Mei H, Meigs JB, Menni C, Nam K, Nolte IM, Pacheco NL, Petty LE, Polikowsky HG, Province MA, Psaty BM, Raffield LM, Raitakari OT, Rich SS, Riha RL, Risch L, Risch M, Ruiz-Narvaez EA, Scott RJ, Sitlani CM, Smith JA, Sofer T, Teder-Laving M, Völker U… See abstract for full author list ➔ Nagarajan P, et al. medRxiv [Preprint]. 2024 Mar 8:2024.03.07.24303870. doi: 10.1101/2024.03.07.24303870. medRxiv. 2024. Update in: Mol Psychiatry. 2025 Aug;30(8):3660-3672. doi: 10.1038/s41380-025-02954-w. PMID: 38496537 Free PMC article. Updated. Preprint.
A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations.
Wang H, Nagarajan P, Winkler T, Bentley A, Miller C, Kraja A, Schwander K, Lee S, Wang W, Brown M, Morrison J, Giri A, O'Connell J, Bartz T, de Las Fuentes L, Gudmundsdottir V, Guo X, Harris S, Huang Z, Kals M, Kho M, Lefevre C, Luan J, Lyytikäinen LP, Mangino M, Milaneschi Y, Palmer N, Rao V, Rauramaa R, Shen B, Stadler S, Sun Q, Tang J, Thériault S, van der Graaf A, van der Most P, Wang Y, Weiss S, Westerman K, Yang Q, Yasuharu T, Zhao W, Zhu W, Altschul D, Ansari MAY, Anugu P, Argoty-Pantoja A, Arzt M, Aschard H, Attia J, Bazzano L, Breyer M, Brody J, Cade B, Chen HH, Chen YI, Chen Z, de Vries P, Dimitrov L, Do A, Du J, Dupont C, Edwards T, Evans M, Faquih T, Felix S, Fisher-Hoch S, Floyd J, Graff M, Charles Gu C, Gu D, Hairston K, Hanley A, Heid I, Heikkinen S, Highland H, Hood M, Kähönen M, Karvonen-Gutierrez C, Kawaguchi T, Kazuya S, Tanika K, Komulainen P, Levy D, Lin H, Liu P, Marques-Vidal P, McCormick J, Mei H, Meigs J, Menni C, Nam K, Nolte I, Pacheco N, Petty L, Polikowsky H, Province M, Psaty B, Raffield L, Raitakari O, Rich S, Riha R, Risch L, Risch M, Ruiz-Narvaez E, Scott R, Sitlani C, Smith J, Sofer T, Teder-Laving M, Völker U, Vollenweider P, Wang G, van Dijk KW,… See abstract for full author list ➔ Wang H, et al. Res Sq [Preprint]. 2024 Jul 17:rs.3.rs-4163414. doi: 10.21203/rs.3.rs-4163414/v1. Res Sq. 2024. Update in: Mol Psychiatry. 2025 Aug;30(8):3660-3672. doi: 10.1038/s41380-025-02954-w. PMID: 39070651 Free PMC article. Updated. Preprint.

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A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

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A large-scale genome-wide study of gene-sleep duration interactions for blood pressure in 811,405 individuals from diverse populations

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Abstract

Conflict of interest statement

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