Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile
Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile
Abstract Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To provide new insights in the biology of sleep-associated adverse lipid profile, we conducted multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identified 49 novel lipid loci, and 10 additional novel lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identified new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The novel gene-sleep interactions had a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explained 4.25% of the variance in triglyceride concentration. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
Marques-Vidal Pedro、Waldenberger Melanie、Martin Lisa W、Homuth Georg、Li Changwei、Tajuddin Salman M、Rankinen Tuomo、Gieger Christian、Kraja Aldi、Dijk Ko Willems van、Yu Caizheng、Zonderman Alan B、Esko T?nu、Grabe Hans J、Bentley Amy R、Sung Yun Ju、Manning Alisa、Brown Michael R、Chen Han、Franceschini Nora、Uitterlinden Andr¨| G、Xiang Yong-Bing、Evans Michele K、Gudnason Vilmundur、Kelly Tanika N、Psaty Bruce M、Rotimi Charles、Adolfo Correa、Ballantyne Christie、Boerwinkle Eric、Dimou Niki、Gharib Sina A、Haba-Rubio Jos¨|、Heinzer Rapha?l、Luik Annemarie I、Milaneschi Yuri、Peyser Patricia、Reiner Alex P、Schreiner Pamela J、Sidney Stephen S、Sims Mario、Sofer Tamar、Swertz Morris A、de las Fuentes Lisa、Horimoto Andrea R、Ilkov Marjan、Kho Minjung、Lim Elise、Wang Zhe、Marten Jonathan、Laville Vincent、Alver Maris、Palmer Nicholette D、Weiss Stefan、Lehtim?ki Terho、Fox Ervin F、Kooperberg Charles、Rao Dabeeru C、Redline Susan、Evangelou Evangelos、Raitakari Olli T、Taylor Kent D、Harris Tamara B、Mook-Kanamori Dennis O、Gottlieb Daniel J、Rich Stephen S、Heikkinen Sami、Province Mike、Roenneberg Till、Shikany James、K¨1hnel Brigitte、Gauderman W James、Sitlani Colleen M、Aschard Hugues、Rauramaa Rainer、Eiriksdottir Gudny、Gao Chuan、Winkler Thomas W、Vollenweider Peter、Penninx Brenda WJH、Vojinovic Dina、Nalls Mike A、Zheng Wei、van der Spek Ashley、Wu Tangchun、Elliott Paul、de Vries Paul S、He Meian、North Kari E、Bos Maxime M、Rensen Patrick CN、Rice Treva K、Arnett Donna K、Amin Najaf、Kilpel?inen Tuomas O.、Wen Wanqing、Metspalu Andres、Wallance Robert B、Rotter Jerome I、Krieger Jose E、Liu Yongmei、Schwander Karen、Guo Xiuqing、Noordam Raymond、Becker Diane M、Richard Melissa、Zhu Xiaofeng、Feitosa Mary、Shu Xiao-Ou、Strauch Konstantin、Lyytik?inen Leo-Pekka、Kritchevsky Stephen B、Study Lifelines Cohort、Hixson James E、Pereira Alexandre C、Cade Brian E、Wang Heming、Lee Jiwon、Ikram M Arfan、Nolte Ilja M、Rice Kenneth、Liu Ching-Ti、Snieder Harold、Bouchard Claude、Duijn Cornelia M van、Cupples L Adrienne、Fornage Myriam、Meitinger Thomas、Liu Jingmin、Lohman Kurt K、Heemst Diana van、Bielak Larry、O?ˉConnell Jeff、Peters Annette、Bartz Traci M、V?lzke Henry、Kardia Sharon、Munroe Patricia B、Lakka Timo A、Morrison Alanna C、Musani Solomon K、Graff Maria E、Aslibekyan Stella、Loos Ruth JF、M?gi Reedik、Wagenknecht Lynne E、Biermasz Nienke R、Yanek Lisa R、Komulainen Pirjo
Medicine, Internal Medicine, Lausanne University HospitalResearch 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 Health||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceCardiology, School of Medicine and Health Sciences, George Washington UniversityInterfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine GreifswaldEpidemiology and Biostatistics, University of Georgia at Athens College of Public HealthHealth Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthHuman 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 Statistical Genomics, Department of Genetics, Washington University School of MedicineDepartment of Internal Medicine, Division of Endocrinology, Leiden University Medical Center||Department of Human Genetics, Leiden University Medical CenterDepartment of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and TechnologyBehavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthEstonian Genome Center, Institute of Genomics, University of Tartu||Broad Institute of the Massachusetts Institute of Technology and Harvard UniversityDepartment Psychiatry and Psychotherapy, University Medicine GreifswaldCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthDivision of Biostatistics, Washington University School of MedicineClinical and Translational Epidemiology Unit, Massachusetts General Hospital||Department of Medicine, Harvard Medical SchoolHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonHuman 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 HoustonDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaDepartment of Epidemiology, Erasmus University Medical Center||Department of Internal Medicine, Erasmus University Medical CenterSKLORG & Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of MedicineHealth Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthIcelandic Heart Association||Faculty of Medicine, University of IcelandEpidemiology, Tulane University School of Public Health and Tropical MedicineCardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington||Kaiser Permanente Washington, Health Research InstituteCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of HealthJackson Heart Study, Department of Medicine, University of Mississippi Medical Center, JacksonSection of Cardiovascular Research, Baylor College of Medicine||Houston Methodist Debakey Heart and Vascular CenterHuman 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 MedicineDepartment of Hygiene and Epidemiology, University of Ioannina Medical SchoolComputational Medicine Core, Center for Lung Biology, UW Medicine Sleep Center, Medicine, University of WashingtonMedicine, Sleep Laboratory, Lausanne University HospitalMedicine, Sleep Laboratory, Lausanne University HospitalDepartment of Epidemiology, Erasmus University Medical CenterCardiology, School of Medicine and Health Sciences, George Washington UniversityDepartment of Epidemiology, School of Public Health, University of MichiganFred Hutchinson Cancer Research Center, University of Washington School of Public HealthDivision of Epidemiology & Community Health, School of Public Health, University of MinnesotaDivision of Research, Kaiser Permanente Northern CaliforniaJackson Heart Study, Department of Medicine, University of Mississippi Medical Center, JacksonDivision of Sleep and Circadian Disorders, Harvard Medical School, Brigham and Women?ˉs Hospital||Institute of Human Genetics, Technische Universit?t M¨1nchenUniversity of Groningen, University Medical Center Groningen, Department of GeneticsCardiovascular Division, Department of Medicine, Washington University School of Medicine||Division of Biostatistics, Washington University School of MedicineLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of S?o Paulo Medical SchoolIcelandic Heart AssociationDepartment of Epidemiology, School of Public Health, University of MichiganDepartment 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 HoustonMedical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of EdinburghCentre de Bioinformatique, Biostatistique et Biologie Int¨|grative (C3BI), Institut PasteurEstonian Genome Center, Institute of Genomics, University of Tartu||Department of Biotechnology, Institute of Molecular and Cell Biology, University of TartuBiochemistry, Wake Forest School of Medicine, Winston-SalemInterfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine GreifswaldDepartment of Clinical Chemistry, Fimlab Laboratories||Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Technology, Tampere UniversityCardiology, Medicine, University of Mississippi Medical CenterFred Hutchinson Cancer Research Center, University of Washington School of Public HealthDivision of Biostatistics, Washington University School of MedicineDivision of Sleep and Circadian Disorders, Harvard Medical School, Brigham and Women?ˉs Hospital||Division of Pulmonary Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical SchoolDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London||Department of Hygiene and Epidemiology, University of Ioannina Medical SchoolDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital||University of TurkuGenomic Outcomes, Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical CenterLaboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of HealthDepartment of Clinical Epidemiology, Leiden University Medical Center,||Department of Public Health and Primary Care, Leiden University Medical CenterDepartment of Medicine, Harvard Medical School||Division of Sleep and Circadian Disorders, Harvard Medical School, Brigham and Women?ˉs Hospital||VA Boston Healthcare SystemCenter for Public Health Genomics, University of VirginiaInstitute of Clinical Medicine, Internal Medicine, University of Eastern Finland||Institute of Biomedicine, School of Medicine, University of Eastern FinlandDivision of Statistical Genomics, Department of Genetics, Washington University School of MedicineInstitute of Medical Psychology, Ludwig-Maximilians-Universitat MunchenDivision of Preventive Medicine, Department of Medicine, University of Alabama at BirminghamResearch 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 HealthBiostatistics, Preventive Medicine, University of Southern CaliforniaCardiovascular Health Research Unit, Medicine, University of WashingtonDepartment of Epidemiology, Harvard School of Public Health||Centre de Bioinformatique, Biostatistique et Biologie Int¨|grative (C3BI), Institut PasteurFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise MedicineIcelandic Heart AssociationMolecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-SalemDepartment of Genetic Epidemiology, University of RegensburgMedicine, Internal Medicine, Lausanne University HospitalDepartment of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research InstituteDepartment of Epidemiology, Erasmus University Medical CenterLaboratory of Neurogenetics, National Institute on Aging||Data Tecnica International, Glen EchoDivision of Epidemiology, Department of Medicine, Vanderbilt University School of MedicineDepartment of Epidemiology, Erasmus University Medical CenterDepartment of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu||MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London||National Institute of Health Research Imperial College London Biomedical Research Centre||UK-DRI Dementia Research Institute at Imperial College LondonHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonDepartment of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical CenterDepartment of Internal Medicine, Division of Endocrinology, Leiden University Medical CenterDivision of Biostatistics, Washington University School of MedicineDean?ˉs Office, University of Kentucky College of Public HealthDepartment of Epidemiology, Erasmus 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 SinaiDivision of Epidemiology, Department of Medicine, Vanderbilt University School of MedicineEstonian Genome Center, Institute of Genomics, University of Tartu||Department of Biotechnology, Institute of Molecular and Cell Biology, University of TartuDepartment of Epidemiology, University of Iowa College of Public HealthGenomic Outcomes, Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical CenterLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of S?o Paulo Medical SchoolPublic Health Sciences, Epidemiology and Prevention, Wake Forest University Health SciencesDivision of Biostatistics, Washington University School of MedicineGenomic Outcomes, Department of Pediatrics, Institute for Translational Genomics and Population Sciences, LABioMed at Harbor-UCLA Medical CenterDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical CenterDivision of General Internal Medicine, Department of Medicine, Johns Hopkins University School of MedicineBrown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at HoustonDepartment of Population Quantitative and Health Sciences, Case Western Reserve UniversityDivision of Statistical Genomics, Department of Genetics, Washington University School of MedicineDivision of Epidemiology, Department of Medicine, Vanderbilt University School of MedicineInstitute of Genetic Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||Institute for Medical Informatics Biometry and Epidemiology, Ludwig-Maximilians-Universitat MunchenDepartment of Clinical Chemistry, Fimlab Laboratories||Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Technology, Tampere UniversitySticht Center for Healthy Aging and Rehabilitation, Gerontology and Geriatric Medicine, Wake Forest School of MedicineLifelines CohortHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonLaboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of S?o Paulo Medical SchoolDivision of Sleep and Circadian Disorders, Harvard Medical School, Brigham and Women?ˉs HospitalDivision of Sleep and Circadian Disorders, Harvard Medical School, Brigham and Women?ˉs HospitalDivision of Sleep and Circadian Disorders, Harvard Medical School, Brigham and Women?ˉs HospitalDepartment of Epidemiology, Erasmus University Medical Center||Department of Radiology and Nuclear Medicine, Erasmus University Medical CenterUniversity of Groningen, University Medical Center Groningen, Department of EpidemiologyDepartment of Biostatistics, University of WashingtonDepartment of Biostatistics, Boston University School of Public HealthUniversity of Groningen, University Medical Center Groningen, Department of EpidemiologyHuman Genomics Laboratory, Pennington Biomedical Research CenterDepartment of Epidemiology, Erasmus University Medical Center||Nuffield Department of Population Health, University of OxfordDepartment of Biostatistics, Boston University School of Public Health||NHLBI Framingham Heart Study, FraminghamBrown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at HoustonInstitute of Human Genetics, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental HealthFred Hutchinson Cancer Research Center, University of Washington School of Public HealthPublic Health Sciences, Biostatistical Sciences, Wake Forest University Health SciencesDepartment of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical CenterDepartment of Epidemiology, School of Public Health, University of MichiganDivision of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine||Program for Personalized and Genomic Medicine, University of Maryland School of MedicineInstitute of Epidemiology, Helmholtz Zentrum M¨1nchen, German Research Center for Environmental Health||DZHK (German Centre for Cardiovascular Research), partner site Munich Heart AllianceCardiovascular Health Research Unit, Biostatistics and Medicine, University of WashingtonInstitute for Community Medicine, University Medicine GreifswaldDepartment of Epidemiology, School of Public Health, University of MichiganClinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London||NIHR Barts Cardiovascular Biomedical Research Centre, Queen Mary University of LondonFoundation 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 Phsiology and Nuclear Medicine, Kuopia University HospitalHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonJackson Heart Study, Department of Medicine, University of Mississippi Medical Center, JacksonDepartment of Epidemiology, Gillings School of Global Public Health, University of North CarolinaDepartment of Epidemiology, University of Alabama at BirminghamThe Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai||The Mindich Child Health Development Institute, The Icahn School of Medicine at Mount SinaiEstonian Genome Center, Institute of Genomics, University of TartuPublic Health Sciences, Wake Forest School of Medicine, Winston-SalemDepartment of Internal Medicine, Division of Endocrinology, Leiden University Medical CenterDivision of General Internal Medicine, Department of Medicine, Johns Hopkins University School of MedicineFoundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine
基础医学生物科学研究方法、生物科学研究技术生理学
Marques-Vidal Pedro,Waldenberger Melanie,Martin Lisa W,Homuth Georg,Li Changwei,Tajuddin Salman M,Rankinen Tuomo,Gieger Christian,Kraja Aldi,Dijk Ko Willems van,Yu Caizheng,Zonderman Alan B,Esko T?nu,Grabe Hans J,Bentley Amy R,Sung Yun Ju,Manning Alisa,Brown Michael R,Chen Han,Franceschini Nora,Uitterlinden Andr¨| G,Xiang Yong-Bing,Evans Michele K,Gudnason Vilmundur,Kelly Tanika N,Psaty Bruce M,Rotimi Charles,Adolfo Correa,Ballantyne Christie,Boerwinkle Eric,Dimou Niki,Gharib Sina A,Haba-Rubio Jos¨|,Heinzer Rapha?l,Luik Annemarie I,Milaneschi Yuri,Peyser Patricia,Reiner Alex P,Schreiner Pamela J,Sidney Stephen S,Sims Mario,Sofer Tamar,Swertz Morris A,de las Fuentes Lisa,Horimoto Andrea R,Ilkov Marjan,Kho Minjung,Lim Elise,Wang Zhe,Marten Jonathan,Laville Vincent,Alver Maris,Palmer Nicholette D,Weiss Stefan,Lehtim?ki Terho,Fox Ervin F,Kooperberg Charles,Rao Dabeeru C,Redline Susan,Evangelou Evangelos,Raitakari Olli T,Taylor Kent D,Harris Tamara B,Mook-Kanamori Dennis O,Gottlieb Daniel J,Rich Stephen S,Heikkinen Sami,Province Mike,Roenneberg Till,Shikany James,K¨1hnel Brigitte,Gauderman W James,Sitlani Colleen M,Aschard Hugues,Rauramaa Rainer,Eiriksdottir Gudny,Gao Chuan,Winkler Thomas W,Vollenweider Peter,Penninx Brenda WJH,Vojinovic Dina,Nalls Mike A,Zheng Wei,van der Spek Ashley,Wu Tangchun,Elliott Paul,de Vries Paul S,He Meian,North Kari E,Bos Maxime M,Rensen Patrick CN,Rice Treva K,Arnett Donna K,Amin Najaf,Kilpel?inen Tuomas O.,Wen Wanqing,Metspalu Andres,Wallance Robert B,Rotter Jerome I,Krieger Jose E,Liu Yongmei,Schwander Karen,Guo Xiuqing,Noordam Raymond,Becker Diane M,Richard Melissa,Zhu Xiaofeng,Feitosa Mary,Shu Xiao-Ou,Strauch Konstantin,Lyytik?inen Leo-Pekka,Kritchevsky Stephen B,Study Lifelines Cohort,Hixson James E,Pereira Alexandre C,Cade Brian E,Wang Heming,Lee Jiwon,Ikram M Arfan,Nolte Ilja M,Rice Kenneth,Liu Ching-Ti,Snieder Harold,Bouchard Claude,Duijn Cornelia M van,Cupples L Adrienne,Fornage Myriam,Meitinger Thomas,Liu Jingmin,Lohman Kurt K,Heemst Diana van,Bielak Larry,O?ˉConnell Jeff,Peters Annette,Bartz Traci M,V?lzke Henry,Kardia Sharon,Munroe Patricia B,Lakka Timo A,Morrison Alanna C,Musani Solomon K,Graff Maria E,Aslibekyan Stella,Loos Ruth JF,M?gi Reedik,Wagenknecht Lynne E,Biermasz Nienke R,Yanek Lisa R,Komulainen Pirjo.Multi-ancestry analysis of gene-sleep interactions in 126,926 individuals identifies multiple novel blood lipid loci that contribute to our understanding of sleep-associated adverse blood lipid profile[EB/OL].(2025-03-28)[2025-06-07].https://www.biorxiv.org/content/10.1101/559393.点此复制
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