Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure
Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure
Abstract Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups using 1 degree of freedom (1df) interaction and 2df joint tests. Primary multi-ancestry analyses in 62,969 individuals in stage 1 identified 3 novel loci that were replicated in an additional 59,296 individuals in stage 2, including rs7955964 (FIGNL2/ANKRD33) showing significant 1df interactions with long sleep duration and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) showing significant 1df interactions with short sleep duration (Pint < 5×10?8). Secondary ancestry-specific two-stage analyses and combined stage 1 and 2 analyses additionally identified 23 novel loci that need external replication, including 3 and 5 loci showing significant 1df interactions with long and short sleep duration, respectively (Pint < 5×10?8). Multiple genes mapped to our 26 novel loci have known functions in sleep-wake regulation, nervous and cardiometabolic systems. We also identified new gene by long sleep interactions near five known BP loci (≤1Mb) including NME7, FAM208A, MKLN1, CEP164, and RGL3/ELAVL3 (Pint < 5×10?8). This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
Guo Xiuqing、He Jiang、Noordam Raymond、Munroe Patricia B、Weiss Stefan、Barac Ana、Rice Treva K、Yao Jie、Wang Heming、Schwander Karen、Winkler Thomas W、Mook-Kanamori Dennis O、Heikkinen Sami、M?gi Reedik、Nolte Ilja M、Metspalu Andres、Arking Dan E、Chen Han、Wen Wanqing、O?ˉConnell Jeff、Eiriksdottir Gudny、Milaneschi Yuri、Penninx Brenda WJH、Gauderman James、Gao Chuan、Waldenberger Melanie、Peters Annette、Kelly Tanika N、Evans Michele K、Bouchard Claude、North Kari E、Harris Sarah E、Horimoto Andrea R、Vojinovic Dina、Musani Solomon K、Mukherjee Sutapa、K?h?nen Mika、Zheng Wei、Pereira Alexandre C、Psaty Bruce M、van Duijn Cornelia M、Lee Jiwon、Aschard Hugues、Fornage Myriam、Redline Susan、Krieger Jose E、Sidney Stephen S、Bis Joshua C、Ikram M Arfan、Amin Najaf、Schreiner Pamela J、Wilson Gregory、Kooperberg Charles、Brown Michael R、Lehtim?ki Terho、D?rr Marcus、Ilkov Marjan、Manning Alisa K、Lyytik?inen Leo-Pekka、Strauch Konstantin、Franceschini Nora、Boerwinkle Eric、Esko T?nu、Milani Lili、Bartz Traci M、Palmer Lyle J、Lakka Timo A、Shikany James M、Liu Yongmei、Hall Kelly A、Gottlieb Daniel、Rauramaa Rainer、Martin Lisa W、Starr John M、Palmer Nicholette D、Wagenknecht Lynne E、van der Most Peter J、Sofer Tamar、Rich Stephen S、Chen Yii-Der Ida、Grabe Hans J、Zhu Xiaofeng、Deary Ian J、Nierenberg Jovia L、Zonderman Alan B、Uitterlinden Andr¨| G、Alver Maris、Waken RJ、Roenneberg Till、Xu Hanfei、Levy Daniel、Launer Lenore J、Hillman David R、Luik Annemarie I、Kilpel?inen Tuomas O、Komulainen Pirjo、V?lker Uwe、Richard Melissa、Shu Xiao-Ou、de Vries Paul S、K¨1hnel Brigitte、Gudnason Vilmundur、Rao Dabeeru C、Wallace Robert B、Chitrala Kumaraswamynaidu、Rice Kenneth、Lohman Kurt K、Zee Phyllis、Gharib Sina A、Cade Brian E、Lim Elise、Biermasz Nienke R、Meitinger Thomas、Palmas Walter、Fox Ervin R、van Heemst Diana、Bentley Amy R.、Liu Ching-Ti、Morrison Alanna C、Rankinen Tuomo、Gieger Christian、Sung Yun Ju、Rotter Jerome I、Snieder Harold、Sims Mario
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment of Epidemiology, Tulane University School of Public Health and Tropical MedicineDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical CenterClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London||National Institute for Health Research Barts Cardiovascular Biomedical Research Unit, Queen Mary University of LondonInterfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald||German Center for Cardiovascular Research (DZHK), partner site GreifswaldMedStar Heart and Vascular InstituteDivision of Biostatistics, Washington University School of MedicineThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDivision of Sleep and Circadian Disorders, Brigham and Women?ˉs Hospital, Harvard Medical School||Program in Medical and Population Genetics, Broad InstituteDivision of Biostatistics, Washington University School of MedicineDepartment of Genetic Epidemiology, University of RegensburgDepartment of Clinical Epidemiology, Leiden University Medical Center||Department of Public Health and Primary Care, Leiden University Medical CenterInstitute of Biomedicine, School of Medicine, University of Eastern Finland||Institute of Clinical Medicine, Internal Medicine, University of Eastern FinlandEstonian Genome Center, Institute of Genomics, University of TartuDepartment of Epidemiology, University of Groningen, University Medical Center GroningenEstonian Genome Center, Institute of Genomics, University of TartuMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of MedicineHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston||Center for Precision Health, School of Public Health & School of Biomedical Informatics, The University of Texas Health Science Center at HoustonDivision of Epidemiology, Department of Medicine, Vanderbilt University School of MedicineDivision of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine||Program for Personalized and Genomic Medicine, University of Maryland School of MedicineIcelandic Heart AssociationDepartment of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije UniversiteitDepartment of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije UniversiteitBiostatistics, Preventive Medicine, University of Southern CaliforniaMolecular Genetics and Genomics Program, Wake Forest School of MedicineResearch Unit of Molecular Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||Institute of Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental HealthInstitute of Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||German Centre for Cardiovascular Research (DZHK), partner site Munich Heart AllianceDepartment of Epidemiology, Tulane University School of Public Health and Tropical MedicineLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthHuman Genomics Laboratory, Pennington Biomedical Research CenterDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaLothian Birth Cohorts group, Department of Psychology, University of EdinburghLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of S?o Paulo Medical SchoolDepartment of Epidemiology, Erasmus MC, University Medical Center||Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical CenterDepartment of Medicine, University of Mississippi Medical CenterSleep Health Service, Respiratory and Sleep Services, Southern Adelaide Local Health Network||Adelaide Institute for Sleep Health, Flinders UniversityDepartment of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere University||Department of Clinical Physiology, Tampere University HospitalDivision of Epidemiology, Department of Medicine, Vanderbilt University School of MedicineLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of S?o Paulo Medical School||Department of Genetics, Harvard Medical SchoolCardiovascular Health Research Unit, Departments of Epidemiology, Medicine and Health Services, University of Washington||Kaiser Permanente Washington Health Research InstituteDepartment of Epidemiology, Erasmus MC, University Medical Center||Nuffield Department of Population Health, University of OxfordDivision of Sleep and Circadian Disorders, Brigham and Women?ˉs Hospital, Harvard Medical SchoolDepartment of Epidemiology, Harvard School of Public Health||Centre de Bioinformatique, Biostatistique et Biologie Int¨|grative (C3BI), Institut PasteurHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston||Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at HoustonDivision of Sleep and Circadian Disorders, Brigham and Women?ˉs Hospital, Harvard Medical School||Division of Pulmonary Medicine, Department of Medicine, Beth Israel Deaconess Medical CenterLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of S?o Paulo Medical SchoolKaiser Permanente Northern CaliforniaCardiovascular Health Research Unit, Department of Medicine, University of WashingtonDepartment of Epidemiology, Erasmus MC, University Medical Center||Department of Radiology and Nuclear Medicine, Erasmus University Medical CenterDepartment of Epidemiology, Erasmus MC, University Medical CenterDivision of Epidemiology & Community Health, School of Public Health, University of MinnesotaJHS Graduate Training and Education Center, Jackson State UniversityDivision of Public Health Sciences, Fred Hutchinson Cancer Research CenterHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonDepartment of Clinical Chemistry, Fimlab Laboratories||Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere UniversityGerman Center for Cardiovascular Research (DZHK), partner site Greifswald||Department of Internal Medicine B, University Medicine GreifswaldIcelandic Heart AssociationProgram in Medical and Population Genetics, Broad Institute||Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Clinical Chemistry, Fimlab Laboratories||Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, Tampere UniversityInstitute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University||Institute of Genetic Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental HealthDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston||Human Genome Sequencing Center, Baylor College of MedicineEstonian Genome Center, Institute of Genomics, University of TartuEstonian Genome Center, Institute of Genomics, University of TartuCardiovascular Health Research Unit, Departments of Biostatistics and Medicine, University of WashingtonSchool of Public Health, The University of AdelaideFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine||Institute of Biomedicine, School of Medicine, University of Eastern Finland||Department of Clinical Physiology and Nuclear Medicine, Kuopio University HospitalDivision of Preventive Medicine, School of Medicine, University of Alabama at BirminghamDivision of Cardiology, Department of Medicine, Duke Molecular Physiology Institute Duke University School of MedicineSchool of Public Health, The University of AdelaideDivision of Sleep and Circadian Disorders, Brigham and Women?ˉs Hospital, Harvard Medical SchoolFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise MedicineGeorge Washington University School of Medicine and Health SciencesAlzheimer Scotland Dementia Research Centre, The University of EdinburghBiochemistry, Wake Forest School of MedicinePublic Health Sciences, Wake Forest School of MedicineDepartment of Epidemiology, University of Groningen, University Medical Center GroningenDivision of Sleep and Circadian Disorders, Brigham and Women?ˉs Hospital, Harvard Medical School||Program in Medical and Population Genetics, Broad InstituteCenter for Public Health Genomics, University of VirginiaThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment Psychiatry and Psychotherapy, University Medicine GreifswaldDepartment of Population and Quantitative Health Sciences, Case Western Reserve UniversityLothian Birth Cohorts group, Department of Psychology, University of EdinburghDepartment of Epidemiology, Tulane University School of Public Health and Tropical MedicineLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthDepartment of Epidemiology, Erasmus MC, University Medical CenterEstonian Genome Center, Institute of Genomics, University of Tartu||Department of Genetic Medicine and Development, University of GenevaField and Environmental Data ScienceInstitute of Medical Psychology, Ludwig-Maximilians-Universit?t M¨1nchenDepartment of Biostatistics, Boston University School of Public HealthDepartment of Biostatistics, Boston University School of Public Health||Population Sciences Branch, National Heart, Lung, and Blood Institute Framingham Heart StudyLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthDepartment of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner HospitalDepartment of Epidemiology, Erasmus MC, University Medical CenterNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen||Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount SinaiFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise MedicineInterfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine Greifswald||German Center for Cardiovascular Research (DZHK), partner site GreifswaldBrown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at HoustonDivision of Epidemiology, Department of Medicine, Vanderbilt University School of MedicineHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonResearch Unit of Molecular Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||Institute of Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental HealthIcelandic Heart Association||Faculty of Medicine, University of IcelandDivision of Biostatistics, Washington University School of MedicineDepartment of Epidemiology, University of Iowa College of Public HealthLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthDepartment of Biostatistics, University of WashingtonDivision of Cardiology, Department of Medicine, Duke Molecular Physiology Institute Duke University School of MedicineDepartment of Neurology, Northwestern UniversityComputational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Department of Medicine, University of WashingtonDivision of Sleep and Circadian Disorders, Brigham and Women?ˉs Hospital, Harvard Medical School||Program in Medical and Population Genetics, Broad InstituteDepartment of Biostatistics, Boston University School of Public HealthDivision of Endocrinology, Department of Internal Medicine, Leiden University Medical CenterInstitute of Human Genetics, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental HealthDivision of General Medicine, Department of Medicine, Columbia UniversityDepartment of Medicine, University of Mississippi Medical CenterDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical CenterCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthDepartment of Biostatistics, Boston University School of Public HealthHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonHuman Genomics Laboratory, Pennington Biomedical Research CenterResearch Unit of Molecular Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||German Center for Diabetes Research (DZD e.V.)Division of Biostatistics, Washington University School of MedicineThe Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical CenterDepartment of Epidemiology, University of Groningen, University Medical Center GroningenDepartment of Medicine, University of Mississippi Medical Center
基础医学生理学遗传学
Gene-environment interactionsleepblood pressuremulti-ancestry
Guo Xiuqing,He Jiang,Noordam Raymond,Munroe Patricia B,Weiss Stefan,Barac Ana,Rice Treva K,Yao Jie,Wang Heming,Schwander Karen,Winkler Thomas W,Mook-Kanamori Dennis O,Heikkinen Sami,M?gi Reedik,Nolte Ilja M,Metspalu Andres,Arking Dan E,Chen Han,Wen Wanqing,O?ˉConnell Jeff,Eiriksdottir Gudny,Milaneschi Yuri,Penninx Brenda WJH,Gauderman James,Gao Chuan,Waldenberger Melanie,Peters Annette,Kelly Tanika N,Evans Michele K,Bouchard Claude,North Kari E,Harris Sarah E,Horimoto Andrea R,Vojinovic Dina,Musani Solomon K,Mukherjee Sutapa,K?h?nen Mika,Zheng Wei,Pereira Alexandre C,Psaty Bruce M,van Duijn Cornelia M,Lee Jiwon,Aschard Hugues,Fornage Myriam,Redline Susan,Krieger Jose E,Sidney Stephen S,Bis Joshua C,Ikram M Arfan,Amin Najaf,Schreiner Pamela J,Wilson Gregory,Kooperberg Charles,Brown Michael R,Lehtim?ki Terho,D?rr Marcus,Ilkov Marjan,Manning Alisa K,Lyytik?inen Leo-Pekka,Strauch Konstantin,Franceschini Nora,Boerwinkle Eric,Esko T?nu,Milani Lili,Bartz Traci M,Palmer Lyle J,Lakka Timo A,Shikany James M,Liu Yongmei,Hall Kelly A,Gottlieb Daniel,Rauramaa Rainer,Martin Lisa W,Starr John M,Palmer Nicholette D,Wagenknecht Lynne E,van der Most Peter J,Sofer Tamar,Rich Stephen S,Chen Yii-Der Ida,Grabe Hans J,Zhu Xiaofeng,Deary Ian J,Nierenberg Jovia L,Zonderman Alan B,Uitterlinden Andr¨| G,Alver Maris,Waken RJ,Roenneberg Till,Xu Hanfei,Levy Daniel,Launer Lenore J,Hillman David R,Luik Annemarie I,Kilpel?inen Tuomas O,Komulainen Pirjo,V?lker Uwe,Richard Melissa,Shu Xiao-Ou,de Vries Paul S,K¨1hnel Brigitte,Gudnason Vilmundur,Rao Dabeeru C,Wallace Robert B,Chitrala Kumaraswamynaidu,Rice Kenneth,Lohman Kurt K,Zee Phyllis,Gharib Sina A,Cade Brian E,Lim Elise,Biermasz Nienke R,Meitinger Thomas,Palmas Walter,Fox Ervin R,van Heemst Diana,Bentley Amy R.,Liu Ching-Ti,Morrison Alanna C,Rankinen Tuomo,Gieger Christian,Sung Yun Ju,Rotter Jerome I,Snieder Harold,Sims Mario.Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure[EB/OL].(2025-03-28)[2025-06-28].https://www.biorxiv.org/content/10.1101/2020.05.29.123505.点此复制
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