This is a preprint.

It has not yet been peer reviewed by a journal.

The National Library of Medicine is running a pilot to include preprints that result from research funded by NIH in PMC and PubMed.

[Preprint]. 2024 Mar 8:2024.03.07.24303870.

doi: 10.1101/2024.03.07.24303870.

A Large-Scale Genome-Wide Study of Gene-Sleep Duration Interactions for Blood Pressure in 811,405 Individuals from Diverse Populations

Pavithra Nagarajan¹, Thomas W Winkler², Amy R Bentley³, Clint L Miller^{4

5}, Aldi T Kraja⁶, Karen Schwander⁷, 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 Altschul²², Md Abu Yusuf Ansari⁵⁶, Pramod Anugu⁵⁷, Anna D Argoty-Pantoja⁴³, Michael Arzt³⁸, Hugues Aschard^{58

59}, John R Attia⁶⁰, 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 Dupont⁶¹, Todd L Edwards^{13

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

47}, Stephan B Felix^{46

63}, Susan P Fisher-Hoch⁶⁴, James S Floyd^{15

65}, Mariaelisa Graff⁴⁴, Charles Gu¹⁸, Dongfeng Gu⁶⁶, Kristen G Hairston⁶⁷, Anthony J Hanley⁶⁸, Iris M Heid², Sami Heikkinen⁶⁹, Heather M Highland⁴⁴, Michelle M Hood⁵⁴, Mika Kähönen^{29

70}, Carrie A Karvonen-Gutierrez⁵⁴, Takahisa Kawaguchi⁵², Setoh Kazuya⁵¹, Tanika N Kelly³⁵, Pirjo Komulainen³⁶, Daniel Levy^{71

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

74}, Joseph B McCormick⁶⁴, Hao Mei⁵⁶, James B Meigs^{47

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

65}, Laura M Raffield⁷⁶, Olli T Raitakari^{77

78

79}, Stephen S Rich^{80

81}, 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^{73

74}, Guanchao Wang⁶¹, Ko Willems van Dijk^{9

90}, Otis D Wilson^{13

91}, Rui Xia⁸, Jie Yao²¹, Kristin L Young⁴⁴, Ruiyuan Zhang²³, Xiaofeng Zhu⁹², Jennifer E Below⁵⁵, Carsten A Böger^{93

94

95}, David Conen⁹⁶, Simon R Cox²², Marcus Dörr^{46

63}, Mary F Feitosa⁷, Ervin R Fox⁹⁷, Nora Franceschini⁴⁴, Sina A Gharib⁹⁸, Vilmundur Gudnason^{19

20}, Sioban D Harlow⁵⁴, Jiang He^{23

99}, Elizabeth G Holliday⁶⁰, Zoltan Kutalik^{42

100}, Timo A Lakka^{69

101

102}, Deborah A Lawlor^{49

50}, Seunggeun Lee²⁵, Terho Lehtimäki^{28

29}, Changwei Li²³, 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

92}, Alisa K Manning^{104

105}, James Gauderman¹¹, Han Chen^{10

106}, Patricia B Munroe¹⁰⁷, Dabeeru C Rao¹⁸, Diana van Heemst¹⁰⁸, Susan Redline^{1

47}, Raymond Noordam¹⁰⁸, Heming Wang^{1

47}

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, Charlottesvil le, 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 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, MO, USA.
¹⁸ Center for Biostatistics and Data Science, Institute for Informatics, Data Science, and Biostatistics, Washington University in St. Louis, School of Medicine, 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, US.
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 Finnish Cardiovascular Research Center - Tampere, Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere, Finland.
³⁰ Department of Twin Research, 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, 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, Maryland.
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 Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁷ Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁸ Department of Computational Biology, F-75015 Paris, France Institut Pasteur, Université Paris Cité, Paris, France.
⁵⁹ Department of Epidemiology, Harvard TH School of Public Health, Boston, MA, USA.
⁶⁰ School of Medicine and Public Health, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia.
⁶¹ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶² Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, US A.
⁶³ Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, Un iversity Medicine Greifswald, Greifswald, Germany.
⁶⁴ School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Brownsville, TX, USA.
⁶⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁶⁶ Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science an d Technology, Shenzhen, China.
⁶⁷ Department of Endocrinology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁶⁸ Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
⁶⁹ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Kuopio.
⁷⁰ Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
⁷¹ Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁷² Framingham Heart Study, Framingham, MA, USA.
⁷³ Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁷⁴ Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁷⁵ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁷⁶ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁷⁷ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁷⁸ 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.
⁷⁹ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁸⁰ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁸¹ Department of Public Health 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 Liecht enstein, Vaduz, Liechtenstein.
⁸⁴ Center of Laboratory Medicine, Institute of Clinical Chemistry, University of Bern and Inselspital, Bern, Switze rland.
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 Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
⁹³ Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
⁹⁴ Department of Nephrology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany.
⁹⁵ KfH Kidney Centre Traunstein, Traunstein, Germany.
⁹⁶ Population Health Research Institute, Medicine, McMaster University, Hamilton, On, Canada.
⁹⁷ Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁹⁸ Pulmonary, Critical Care and Sleep Medicine, Medicine, University of Washington, Seattle, WA, USA.
⁹⁹ Tulane University Translational Sciences Institute, New Orleans, LA , 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 Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁰⁷ Clinical Pharmacology and Precision Medicine, Queen Mary University of London, London, UK.
¹⁰⁸ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Lei den, Netherlands.

PMID: 38496537
PMCID: PMC10942520
DOI: 10.1101/2024.03.07.24303870

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. medRxiv. 2024.

[Preprint]. 2024 Mar 8:2024.03.07.24303870.

doi: 10.1101/2024.03.07.24303870.

Authors

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, Charlottesvil le, 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 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, MO, USA.
¹⁸ Center for Biostatistics and Data Science, Institute for Informatics, Data Science, and Biostatistics, Washington University in St. Louis, School of Medicine, 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, US.
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 Finnish Cardiovascular Research Center - Tampere, Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere, Finland.
³⁰ Department of Twin Research, 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, 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, Maryland.
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 Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁷ Jackson Heart Study, University of Mississippi Medical Center, Jackson, MS, USA.
⁵⁸ Department of Computational Biology, F-75015 Paris, France Institut Pasteur, Université Paris Cité, Paris, France.
⁵⁹ Department of Epidemiology, Harvard TH School of Public Health, Boston, MA, USA.
⁶⁰ School of Medicine and Public Health, College of Health Medicine and Wellbeing, University of Newcastle, New Lambton Heights, NSW, Australia.
⁶¹ Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
⁶² Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, US A.
⁶³ Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, Un iversity Medicine Greifswald, Greifswald, Germany.
⁶⁴ School of Public Health, The University of Texas Health Science Center at Houston (UTHealth), Brownsville, TX, USA.
⁶⁵ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁶⁶ Shenzhen Key Laboratory of Cardiovascular Health and Precision Medicine, Southern University of Science an d Technology, Shenzhen, China.
⁶⁷ Department of Endocrinology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
⁶⁸ Department of Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
⁶⁹ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio, Kuopio.
⁷⁰ Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
⁷¹ Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
⁷² Framingham Heart Study, Framingham, MA, USA.
⁷³ Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.
⁷⁴ Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁷⁵ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.
⁷⁶ Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
⁷⁷ Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
⁷⁸ 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.
⁷⁹ Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
⁸⁰ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁸¹ Department of Public Health 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 Liecht enstein, Vaduz, Liechtenstein.
⁸⁴ Center of Laboratory Medicine, Institute of Clinical Chemistry, University of Bern and Inselspital, Bern, Switze rland.
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 Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio, USA.
⁹³ Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
⁹⁴ Department of Nephrology and Rheumatology, Kliniken Südostbayern, Traunstein, Germany.
⁹⁵ KfH Kidney Centre Traunstein, Traunstein, Germany.
⁹⁶ Population Health Research Institute, Medicine, McMaster University, Hamilton, On, Canada.
⁹⁷ Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
⁹⁸ Pulmonary, Critical Care and Sleep Medicine, Medicine, University of Washington, Seattle, WA, USA.
⁹⁹ Tulane University Translational Sciences Institute, New Orleans, LA , 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 Center for Precision Health, McWilliams School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA.
¹⁰⁷ Clinical Pharmacology and Precision Medicine, Queen Mary University of London, London, UK.
¹⁰⁸ Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Lei den, Netherlands.

PMID: 38496537
PMCID: PMC10942520
DOI: 10.1101/2024.03.07.24303870

Update in

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, Chen YI, 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, Vo… See abstract for full author list ➔ Nagarajan P, et al. Mol Psychiatry. 2025 Aug;30(8):3660-3672. doi: 10.1038/s41380-025-02954-w. Epub 2025 Apr 4. Mol Psychiatry. 2025. PMID: 40181193

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 discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management.

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Conflict of interest statement

Conflict of Interest/Disclosures: C.L.M. has received funding from AstraZeneca not related to the current study. B.M.P. serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. D.C. receives consultancy fees from Roche Diagnostics and Trimedics and speaker fees from Servier. D.A.L. has received support from Medtronic LTD and Roche Diagnostics for biomarker research not related to the current study. The remaining authors declare no competing interests.

Figures

**Figure 2.**
Forest Plots of Gene-Sleep Duration Loci Identified by the 1df Interaction Test in Female-Specific Cross-Population Meta-Analyses. These are the prioritized 1df Interaction Test results from female-specific cross-population meta-analyses. Contributing female-specific population groups’ (if this variant is found in the particular population group, after quality control) summary statistics are depicted here that were pooled.

**Figure 3.**
Forest Plots of Gene-Sleep Duration Loci Identified by the 1df Interaction Test in Combined Sex HIS-Specific Meta-Analyses These are the prioritized 1df Interaction Test results from HIS-specific meta-analyses. Other population group data (if this variant is found in the particular population group, after quality control) are shown here to emphasize that these gene-sleep duration interaction loci were significant only in the HIS population group.

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References

1. Makarem N. et al. Sleep Duration and Blood Pressure: Recent Advances and Future Directions. Curr Hypertens Rep 21, 33 (2019). - PMC - PubMed
1. Kanki M. et al. Poor sleep and shift work associate with increased blood pressure and inflammation in UK Biobank participants. Nat Commun 14, 7096 (2023). - PMC - PubMed
1. Kario K. Sleep and nocturnal hypertension: Genes, environment, and individual profiles. J Clin Hypertens (Greenwich) 24, 1263–1265 (2022). - PMC - PubMed
1. Bock J.M., Vungarala S., Covassin N. & Somers V.K. Sleep Duration and Hypertension: Epidemiological Evidence and Underlying Mechanisms. Am J Hypertens 35, 3–11 (2022). - PMC - PubMed
1. Matsubayashi H. et al. Long sleep duration and cardiovascular disease: Associations with arterial stiffness and blood pressure variability. J Clin Hypertens (Greenwich) 23, 496–503 (2021). - PMC - PubMed

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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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