机构：[1]Cardiovascular Division, Department of Medicine, WashingtonUniversity, St. Louis, MO 63110, USA[2]Division of Biostatistics, Washington University School ofMedicine, St. Louis, MO 63110, USA[3]Section of Gerontology and Geriatrics, Department of InternalMedicine, Leiden University Medical Center, Leiden 2333ZA,The Netherlands[4]Department of Genetic Epidemiology, University of Regensburg,93051 Regensburg, Germany[5]Division of Statistical Genomics, Department of Genetics,Washington University School of Medicine, St. Louis, MO 63108,USA[6]Center for Research on Genomics and Global Health, NationalHuman Genome Research Institute, National Institutes of Health,Bethesda, MD 20892, USA[7]Human Genetics Center, Department of Epidemiology, HumanGenetics, and Environmental Sciences, School of Public Health,The University of Texas Health Science Center at Houston,Houston, TX 77030, USA[8]The Institute for Translational Genomics and Population Sciences,Division of Genomic Outcomes, Department of Pediatrics, LosAngeles Biomedical Research Institute at Harbor-UCLA MedicalCenter, Torrance, CA 90502, USA[9]Clinical and Translational Epidemiology Unit, MassachusettsGeneral Hospital, Boston, MA 02114, USA[10]Department of Medicine, Harvard Medical School, Boston, MA02115, USA[11]Division of Preventive Medicine, Brigham and Women’sHospital, Boston, MA 02215, USA[12]Harvard Medical School, Boston, MA 02115, USA[13]Department of Epidemiology, Harvard School of Public Health,Boston, MA 02115, USA[14]Centre de Bioinformatique, Biostatistique et Biologie Intégrative(C3BI), Institut Pasteur, Paris 75724, France[15]Cardiovascular Health Research Unit, Biostatistics and Medicine,University of Washington, Seattle, WA 98101, USA[16]Department of Epidemiology, School of Public Health,University of Michigan, Ann Arbor, MI 48109, USA[17]Centre for Genomic & Experimental Medicine, Institute ofGenetics & Molecular Medicine, University of Edinburgh,Edinburgh EH4 2XU, UK[18]Ocular Epidemiology, Singapore Eye Research Institute,Singapore National Ecy Centre, Singapore 169856, Singapore[19]Ophthalmology & Visual Sciences Academic Clinical Program(Eye ACP), Duke-NUS Medical School, Singapore 169857,Singapore[20]Genome Institute of Singapore, Agency for Science Technologyand Research, Singapore 138672, Singapore[21]Postgraduate Programme in Epidemiology, Federal University ofPelotas, Pelotas, RS 96020-220, Brazil[22]Medical Research Council Integrative Epidemiology Unit,University of Bristol, Bristol BS8 2BN, UK[23]Laboratory of Genetics and Molecular Cardiology, Heart Institute(InCor), University of São Paulo Medical School, São Paulo, SP5403000, Brazil[24]Epidemiology and Biostatistics, University of Georgia at AthensCollege of Public Health, Athens, GA 30602, USA[25]Department of Clinical Epidemiology, Leiden University MedicalCenter, Leiden 2333ZA, Netherlands[26]Public Health Sciences, Epidemiology and Prevention, WakeForest University Health Sciences, Winston-Salem, NC 27157,USA[27]Medical Research Council Human Genetics Unit, Institute ofGenetics and Molecular Medicine, Institute of Genetics andMolecular Medicine, University of Edinburgh, Edinburgh EH42XU, UK[28]Jackson Heart Study, Department of Medicine, University ofMississippi Medical Center, Jackson, MS 39213, USA[29]Clinical Pharmacology, William Harvey Research Institute, Bartsand The London School of Medicine and Dentistry, Queen MaryUniversity of London, London EC1M 6BQ, UK[30]Human Genomics Laboratory, Pennington Biomedical ResearchCenter, Baton Rouge, LA, USA[31]Institute of Molecular Medicine, McGovern Medical School,University of Texas Health Science Center at Houston,Houston, TX 70808, USA[32]Saw Swee Hock School of Public Health, National UniversityHealth System and National University of Singapore,Singapore 117549, Singapore[33]Department of Biostatistics, University of Michigan, Ann Arbor,MI 48109, USA[34]Icelandic Heart Association, Kopavogur 201, Iceland[35]Health Disparities Research Section, Laboratory of Epidemiologyand Population Sciences, National Institute on Aging, NationalInstitutes of Health, Baltimore, MD 21224, USA[36]Department of Public Health Sciences, Loyola UniversityChicago, Maywood, IL 60153, USA[37]Department of Epidemiology, Erasmus University MedicalCenter, Rotterdam, The Netherlands[38]NIHR Barts Cardiovascular Biomedical Research Unit, Barts andThe London School of Medicine and Dentistry, Queen MaryUniversity of London, London, London EC1M 6BQ, UK[39]Biostatistics, Boston University School of Public Health,Boston, MA 02118, USA[40]Estonian Genome Center, Institute of Genomics, University ofTartu, Tartu 51010, Estonia[41]Department of Biotechnology, Institute of Molecular and CellBiology, University of Tartu, Tartu 51010, Estonia[42]CNRS UMR 8199, European Genomic Institute for Diabetes(EGID), Institut Pasteur de Lille, University of Lille, Lille 59000,France[43]Department of Medical Epidemiology and Biostatistics,Karolinska Institutet, Stockholm, Stockholm 17177, Sweden[44]Unit of Epidemiology, Biostatistics and Biodemography,Department of Public Health, Southern Denmark University,Odense 5000, Denmark[45]Biostatistical Sciences, Public Health Sciences, Wake ForestSchool of Medicine, Winston-Salem, NC 27157, USA[46]Department of Epidemiology and Biostatistics, School of PublicHealth, Imperial College London, London W2 1PG, UK[47]Department of Hygiene and Epidemiology, University ofIoannina Medical School, Ioannina 45110, Greece[48]Molecular Genetics and Genomics Program, Wake Forest Schoolof Medicine, Winston-Salem, NC 27157, USA[49]Medical Genetics, Department of Medicine, Surgery and HealthSciences, University of Trieste, Trieste 34100, Italy[50]Institute for Maternal and Child Health–IRCCS “BurloGarofolo”, Trieste 34100, Italy[51]Department of Psychology, Centre for Cognitive Ageing andCognitive Epidemiology, The University of Edinburgh,Edinburgh EH8 9JZ, UK[52]Department of Occupational and Environmental Health and StateKey Laboratory of Environmental Health for Incubating, TongjiMedical College, Huazhong University of Science andTechnology, Wuhan 430030, China[53]Research Unit of Molecular Epidemiology, Helmholtz ZentrumMünchen, German Research Center for Environmental Health,85764 Neuherberg, Germany[54]Institute of Epidemiology, Helmholtz Zentrum München, GermanResearch Center for Environmental Health, 85764Neuherberg, Germany[55]Unit of Cardiovascular and Nutritional Epidemiology, Institute ofEnvironmental Medicine, Karolinska Institutet,Stockholm 17177, Sweden[56]Department of Population and Quantitative Health Sciences, CaseWestern Reserve University, Cleveland, OH 44106, USA[57]Department of Mathematics and Statistics, University ofMinnesota, Duluth, MN 55812, USA[58]Department of Clinical Chemistry, Fimlab Laboratories,Tampere 33520, Finland[59]Department of Clinical Chemistry, Finnish CardiovascularResearch Center - Tampere, Faculty of Medicine and HealthTechnology, University of Tampere, Tampere 33014, Finland[60]University of Groningen, University Medical Center Groningen,Department of Epidemiology, Groningen 9700RB, TheNetherlands[61]Department of Clinical Sciences, Genetic and MolecularEpidemiology Unit, Lund University Diabetes Centre, SkåneUniversity Hospital, Malmö, Skåne 205 02, Sweden[62]Foundation for Research in Health Exercise and Nutrition,Kuopio Research Institute of Exercise Medicine, Kuopio 70100,Finland[63]College of Medicine, Biological Sciences and Psychology, HealthSciences, The Infant Mortality and Morbidity Studies (TIMMS),Leicester LE1 7RH, UK[64]Department of Computational Biology, University of Lausanne,Lausanne 1011, Switzerland[65]Swiss Institute of Bioinformatics, Lausanne 1015, Switzerland[66]Division of Epidemiology, Department of Medicine, VanderbiltUniversity School of Medicine, Nashville, TN 37203, USA[67]Division of Sleep and Circadian Disorders, Brigham andWomen’s Hospital, Boston, MA 02115, USA[68]Department of Gene Diagnostics and Therapeutics, ResearchInstitute, National Center for Global Health and Medicine,Tokyo 1628655, Japan[69]University of Groningen, University Medical Center Groningen,Department of Cardiology, Groningen 9700, The Netherlands[70]Survey Research Center, Institute for Social Research, Universityof Michigan, Ann Arbor, MI 48104, USA[71]Interfaculty Institute for Genetics and Functional Genomics,University Medicine Greifswald, 9713GZ Greifswald, Germany[72]DZHK (German Centre for Cardiovascular Health), Partner SiteGreifswald, 17475 Greifswald, Germany[73]Division of General Internal Medicine, Department of Medicine,Johns Hopkins University School of Medicine, Baltimore, MD21287, USA[74]McKusick-Nathans Institute of Genetic Medicine, Johns HopkinsUniversity School of Medicine, Baltimore, MD 21205, USA[75]Dean’s Office, University of Kentucky College of Public Health,Lexington, KY 40536, USA[76]Human Genome Sequencing Center, Baylor College of Medicine,Houston, TX 77030, USA[77]Cardiovascular Health Research Unit, Medicine, University ofWashington, Seattle, WA 98101, USA[78]Section of Genomic Pediatrics, Department of Pediatrics,Medicine and Physiology, Medical College of Wisconsin,Milwaukee, WI 53226, USA[79]Public Health Sciences, Wake Forest School of Medicine,Winston-Salem, NC 27109, USA[80]Statistics Unit, Singapore Eye Research Institute, SingaporeNational Eye Centre, Singapore 169856, Singapore[81]Ninewells Hospital & Medical School, University of Dundee,Dundee, Scotland DD1 9SY, UK[82]Department of Medicine, Faculty of Medicine, University ofKelaniya, Ragama, Sri Lanka[83]Tropical Metabolism Research Unit, Tropical Medicine ResearchInstitute, University of the West Indies, Mona JMAAW15,Jamaica[84]Cardiology, Medicine, University of Mississippi Medical Center,Jackson, MS 39216, USA[85]Braun School of Public Health, Hebrew University-HadassahMedical Center, Jerusalem 91120, Israel[86]MRC-PHE Centre for Environment and Health, Imperial CollegeLondon, London W2 1PG, UK[87]Cardiovascular Unit, Bioclinicum, Department of Medicine,Karolinska Hospital, Stockholm 17164, Sweden[88]Division of Cardiovascular Medicine, Department of ClinicalSciences, Danderyd University Hospital, Stockholm 18288,Sweden[89]Brigham and Women’s Hospital, Boston, MA 02215, USA[90]Department of Epidemiology, State Key Laboratory ofCardiovascular Disease, Fuwai Hospital, National Center forCardiovascular Diseases, Chinese Academy of Medical Sciencesand Peking Union Medical College, Beijing, China[91]Laboratory of Epidemiology and Population Sciences, NationalInstitute on Aging, National Institutes of Health, Bethesda, MD20892, USA[92]Epidemiology, Tulane University School of Public Health andTropical Medicine, New Orleans, LA 70112, USA[93]Medicine, Tulane University School of Medicine, New Orleans,LA 70112, USA[94]Institute of Biomedicine, School of Medicine, University ofEastern Finland, Kuopio Campus, Kuopio 70211, Finland[95]Institute of Clinical Medicine, Internal Medicine, University ofEastern Finland, Kuopio 70211, Finland[96]Department of Paediatrics, Yong Loo Lin School of Medicine,National University of Singapore, Singapore 119228, Singapore[97]Khoo Teck Puat – National University Children’s MedicalInstitute, National University Health System, Singapore 119228,Singapore[98]Cardiovascular Genetics, Department of Internal Medicine,University of Utah, Salt Lake City, UT 84108, USA[99]Weill Cornell Medicine in Qatar, Doha, Qatar[100]Department of Radiology and Nuclear Medicine, ErasmusUniversity Medical Center, Rotterdam, The Netherlands[101]Department of Biostatistics, University of Alabama atBirmingham, Birmingham, AL 35294, USA[102]Department of Clinical Physiology, Tampere UniversityHospital, Tampere 33521, Finland[103]Department of Clinical Physiology, Finnish CardiovascularResearch Center–Tampere, Faculty of Medicine and HealthTechnology, University of Tampere, Tampere 33014, Finland[104]Department of Biochemistry, National University of Singapore,Singapore 117596, Singapore[105]Novo Nordisk Foundation Center for Basic Metabolic Research,Faculty of Health and Medical Sciences, University ofCopenhagen, Copenhagen DK-2200, Denmark[106]Department of Environmental Medicine and Public Health, TheIcahn School of Medicine at Mount Sinai, New York, NY10029, USA[107]Health Services and Systems Research, Duke-NUS MedicalSchool, Singapore 169857, Singapore[108]Public Health Sciences, Biostatistics and Data Science, WakeForest University Health Sciences, Winston-Salem, NC 27157,USA[109]Institute of Human Genetics, Helmholtz Zentrum München,German Research Center for Environmental Health, 85764Neuherberg, Germany[110]Institute of Human Genetics, Technische Universität München,80333 Munich, Germany[111]Department of Psychiatry, Amsterdam Neuroscience andAmsterdam Public Health Research Institute, VU UniversityMedical Center, Amsterdam 1081 BT, The Netherlands[112]Department of Public Health and Primary Care, LeidenUniversity Medical Center, Leiden 2333ZA, Netherlands[113]Molecular Genetics Section, Laboratory of Neurogenetics,National Institute on Aging, Bethesda, MD 20895, USA[114]Data Tecnica International, Glen Echo, MD 20812, USA[115]Department of Cardiovascular Sciences, University of Leicester,Leicester LE3 9QP, UK[116]NIHR Leicester Biomedical Research Centre, Glenfield Hospital,Leicester LE3 9QP, UK[117]Department of Epidemiology, University of Colorado Denver,Aurora, CO 80045, USA[118]Division of Endocrinology, Diabetes, and Nutrition, Universityof Maryland School of Medicine, Baltimore, MD, USA[119]Program for Personalized and Genomic Medicine, University ofMaryland School of Medicine, Baltimore, MD, USA[120]Department of Medicine, University of Ibadan, Ibadan, Oyo,Nigeria[121]British Heart Foundation Glasgow Cardiovascular ResearchCentre, Institute of Cardiovascular and Medical Sciences,College of Medical, Veterinary and Life Sciences, University ofGlasgow, Glasgow G12 8TA, UK[122]Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA[123]Department of Medicine, Geriatrics Section, Boston MedicalCenter, Boston University School of Medicine, Boston, MA02118, USA[124]DZHK (German Centre for Cardiovascular Research), PartnerSite Munich Heart Alliance, 85764 Neuherberg, Germany[125]Institute of Clinical Chemistry and Laboratory Medicine,University Medicine Greifswald, 17475 Greifswald, Germany[126]University of Split School of Medicine, Split, Croatia[127]University Hospital Split, Split, Croatia[128]Psychiatric Hospital “Sveti Ivan”, Zagreb, Croatia[129]Division of Genetic and Genomic Medicine, Department ofPediatrics, University of California, Irvine, CA 92868, USA[130]Usher Institute of Population Health Sciences and Informatics,University of Edinburgh, Edinburgh EH8 9AG, UK[131]Division of Epidemiology & Community Health, School ofPublic Health, University of Minnesota, Minneapolis, MN55454, USA[132]Division of Preventive Medicine, School of Medicine,University of Alabama at Birmingham, Birmingham, AL 25249,USA[133]Division of Research, Kaiser Permanente of Northern California,Oakland, CA, USA[134]Alzheimer Scotland Dementia Research Centre, The Universityof Edinburgh, Edinburgh EH8 9AZ, UK[135]Centre for Cognitive Ageing and Cognitive Epidemiology, TheUniversity of Edinburgh, Edinburgh, UK[136]Institute of Genetic Epidemiology, Helmholtz ZentrumMünchen, German Research Center for Environmental Health,85764 Neuherberg, Germany[137]Institute of Medical Informatics Biometry and Epidemiology,Ludwig-Maximilians-Universitat Munchen, 80539Munich, Germany[138]University of Groningen, University Medical Center Groningen,Department of Genetics, Groningen 9700RB, The Netherlands[139]Institute for Community Medicine, University MedicineGreifswald, 17475 Greifswald, Germany[140]Department of Internal Medicine, Erasmus University MedicalCenter, Rotterdam, The Netherlands[141]Beijing Institute of Ophthalmology, Beijing Tongren Eye Center,Beijing Ophthalmology and Visual Science Key Lab, BeijingTongren Hospital, Capital Medical University, 100730Beijing, China研究所眼科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院[142]Beijing Tongren Eye Center, Beijing Tongren Hospital, CapitalMedical University, 100730 Beijing, China首都医科大学附属北京同仁医院首都医科大学附属同仁医院[143]Department of Epidemiology, Graduate School of Public Health,University of Pittsburgh, Pittsburgh, PA 15261, USA[144]Division of Cancer Control and Population Sciences, UPMCHillman Cancer, , University of Pittsburgh, Pittsburgh, PA15232, USA[145]Behavioral Epidemiology Section, Laboratory of Epidemiologyand Population Sciences, National Institute on Aging, NationalInstitutes of Health, Baltimore, MD 21224, USA[146]Department of Internal Medicine B, University MedicineGreifswald, 17475 Greifswald, Germany[147]Broad Institute of the Massachusetts Institute of Technology andHarvard University, Boston, MA 02142, USA[148]Section on Nephrology, Department of Internal Medicine, WakeForest School of Medicine, Winston-, Salem, NC 27157, USA[149]Department of Genomics of Common Disease, Imperial CollegeLondon, London W12 0NN, UK[150]German Center for Diabetes Research (DZD e.V.), 85764Neuherberg, Germany[151]Department of Ophthalmology, Medical Faculty Mannheim,University Heidelberg, 68167 Mannheim, Germany[152]Beijing Institute of Ophthalmology, Beijing Ophthalmology andVisual Science Key Lab, Beijing Tongren Eye Center, CapitalMedical University, 100730 Beijing, China研究所眼科研究所首都医科大学附属北京同仁医院首都医科大学附属同仁医院[153]Department of Human Genetics, Graduate School of PublicHealth, University of Pittsburgh, Pittsburgh, PA 15261, USA[154]Department of Clinical Physiology and Nuclear Medicine,Kuopio University Hospital, Kuopio 70211, Finland[155]Lifelines Cohort, Groningen 9700RB, The Netherlands[156]Department of Medicine, Internal Medicine, LausanneUniversity Hospital and University of Lausanne, Lausanne 1011,Switzerland[157]Durrer Center for Cardiogenetic Research, ICIN-NetherlandsHeart Institute, Ultrecht, The Netherlands[158]Faculty of Medicine, University of Iceland, Reykjavik 101,Iceland[159]Sticht Center for Health Aging and Alzheimer’s Prevention,Department of Internal Medicine, Wake Forest School ofMedicine, Winston-Salem, NC 27157, USA[160]NHLBI Framingham Heart Study, Framingham, MA 01702,USA[161]Population Sciences Branch, Division of Intramural Research,National Heart, Lung, and Blood Institute, NIH, Bethesda, MD20892, USA[162]Division of General Medicine, Department of Medicine,Columbia University Medical Center, New York, NY 10032,USA[163]Cardiovascular Health Research Unit, Epidemiology, Medicineand Health Services, University of Washington, Seattle, WA98101, USA[164]Kaiser Permanente Washington Health Research Institute,Seattle, WA 98101, USA[165]Department of Medicine, Yong Loo Lin School of Medicine,National University of Singapore, Singapore 119228, Singapore[166]Nuffield Department of Population Health, University of Oxford,Oxford, UK[167]Department of Biostatistics, University of Washington,Seattle, WA 98195, USA[168]Biostatistics, Preventive Medicine, University of SouthernCalifornia, Los Angeles, CA 90032, USA[169]Epidemiology, University of North Carolina Gilling School ofGlobal Public Health, Chapel Hill, NC 27514, USA[170]Department of Public Health & Clinical Medicine, UmeåUniversity, Umeå, Västerbotten 901 85, Sweden
Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 x 10(-8)). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
基金：
U.S. National Heart, Lung, and Blood Institute (NHLBI), the National Institutes of Health [R01HL118305]; NHLBIUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [K25HL121091]; Novo Nordisk FoundationNovo Nordisk FoundationNovocure Limited [NNF18CC0034900, NNF17OC0026848]; MRCUK Research & Innovation (UKRI)Medical Research Council UK (MRC) [MR/S019669/1, MR/R023484/1, MR/L01341X/1, UKDRI-5001, MC_UU_00007/10] Funding Source: UKRI
第一作者机构：[1]Cardiovascular Division, Department of Medicine, WashingtonUniversity, St. Louis, MO 63110, USA[2]Division of Biostatistics, Washington University School ofMedicine, St. Louis, MO 63110, USA
通讯作者：
通讯机构：[1]Cardiovascular Division, Department of Medicine, WashingtonUniversity, St. Louis, MO 63110, USA[2]Division of Biostatistics, Washington University School ofMedicine, St. Louis, MO 63110, USA
推荐引用方式(GB/T 7714)：
Lisa de las Fuentes,Yun Ju Sung,Raymond Noordam,et al.Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci[J].MOLECULAR PSYCHIATRY.2021,26(6):2111-2125.doi:10.1038/s41380-020-0719-3.
APA：
Lisa de las Fuentes,Yun Ju Sung,Raymond Noordam,Thomas Winkler,Mary F. Feitosa...&Myriam Fornage.(2021).Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci.MOLECULAR PSYCHIATRY,26,(6)
MLA：
Lisa de las Fuentes,et al."Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci".MOLECULAR PSYCHIATRY 26..6(2021):2111-2125
医学