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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
Molecular Psychiatry, Volume 26, No. 6, Year 2021
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Description
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 × 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. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
Authors & Co-Authors
de las Fuentes, Lisa
United States, St. Louis
Washington University in St. Louis
United States, St. Louis
Washington University School of Medicine in St. Louis
Sung, Yunju
United States, St. Louis
Washington University School of Medicine in St. Louis
Noordam, Raymond
Netherlands, Leiden
Leids Universitair Medisch Centrum
Winkler, Thomas W.
Germany, Regensburg
Universität Regensburg
Feitosa, Mary Furlan
United States, St. Louis
Washington University School of Medicine in St. Louis
Schwander, Karen L.
United States, St. Louis
Washington University School of Medicine in St. Louis
Bentley, Amy Rebecca
United States, Bethesda
National Institutes of Health Nih
Brown, Michael R.
United States, Houston
University of Texas Health Science Center at Houston
Guo, Xiuqing
United States, Torrance
Harbor-ucla Medical Center
Manning, Alisa Knodle
United States, Boston
Massachusetts General Hospital
United States, Boston
Harvard Medical School
Chasman, Daniel I.
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard Medical School
Aschard, Hugues
United States, Boston
Harvard T.h. Chan School of Public Health
France, Paris
Institut Pasteur, Paris
Bartz, Traci M.
United States, Seattle
University of Washington
Bielak, Lawrence F.
United States, Ann Arbor
University of Michigan, Ann Arbor
Campbell, Archie I.
United Kingdom, Edinburgh
The University of Edinburgh
Cheng, Ching Yu
Singapore, Singapore City
Singapore Eye Research Institute
Singapore, Singapore City
Duke-nus Medical School
Dorajoo, R. S.O.
Singapore, Singapore City
Agency for Science, Technology and Research, Singapore
Hartwig, Fernando Pires
Brazil, Pelotas
Universidade Federal de Pelotas
United Kingdom, Bristol
Mrc Integrative Epidemiology Unit
Li, Changwei
United States, Athens
University of Georgia
Li-Gao, Ruifang
Netherlands, Leiden
Leids Universitair Medisch Centrum
Liu, Yongmei
United States, Winston Salem
Wake Forest University Health Sciences
Marten, Jonathan
United Kingdom, Edinburgh
Mrc Human Genetics Unit
Musani, Solomon K.
Unknown Affiliation
Ntalla, Ioanna
United Kingdom, London
Queen Mary University of London
Richard, Melissa A.
United States, Houston
University of Texas Health Science Center at Houston
Sim, Xueling
Singapore, Singapore City
National University of Singapore
Smith, Albert Vernon
United States, Ann Arbor
University of Michigan, Ann Arbor
Iceland, Kopavogur
Icelandic Heart Association
Tajuddin, Salman M.
United States, Bethesda
National Institutes of Health Nih
Tayo, Bamidele O.
United States, Chicago
Loyola University Chicago
Vojinovic, Dina
Netherlands, Rotterdam
Erasmus Mc
Warren, Helen R.
United Kingdom, London
Queen Mary University of London
Alver, Maris
Estonia, Tartu
Tartu Ülikool
Boissel, Mathilde
France, Lille
Institut Pasteur de Lille
Chai, Jinfang
Singapore, Singapore City
National University of Singapore
Christensen, Kaare
Denmark, Odense
Syddansk Universitet
Divers, Jasmin
United States, Winston Salem
Wake Forest University School of Medicine
Evangelou, Evangelos
United Kingdom, London
Imperial College London
Greece, Ioannina
Faculty of Medicine
Girotto, Giorgia G.
Italy, Trieste
Università Degli Studi Di Trieste
Italy, Trieste
Irccs Burlo Garofolo
Harris, Sarah E.
United Kingdom, Edinburgh
The University of Edinburgh
Hsu, Fangchi
United States, Winston Salem
Wake Forest University School of Medicine
Kühnel, Brigitte
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Lyytikäinen, Leo Pekka
Finland, Tampere
Fimlab Laboratoriot oy
Finland, Tampere
Tampere University
Nolte, Ilja Maria
Netherlands, Groningen
Rijksuniversiteit Groningen
Poveda, Alaitz
Sweden, Lund
Skånes Universitetssjukhus
Rauramaa, Rainer
Finland, Kuopio
Itä-suomen Yliopisto
Riaz, Muhammad B.
United Kingdom, Leicester
Leicester Medical School
Rueedi, Rico
Switzerland, Lausanne
Université de Lausanne Unil
Switzerland, Lausanne
Sib Swiss Institute of Bioinformatics
Shu, Xiaoou
United States, Nashville
Vanderbilt University School of Medicine
Snieder, Harold
Netherlands, Groningen
Rijksuniversiteit Groningen
Sofer, Tamar
United States, Boston
Brigham and Women's Hospital
Takeuchi, Fumihiko
Japan, Tokyo
National Center for Global Health and Medicine
Verweij, Niek
Netherlands, Groningen
Rijksuniversiteit Groningen
Ware, Erin B.
United States, Ann Arbor
University of Michigan, Ann Arbor
Weiss, Stefan
Germany, Greifswald
Universitätsmedizin Greifswald
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Yanek, Lisa R.
United States, Baltimore
Johns Hopkins School of Medicine
Amin, Najaf A.
Netherlands, Rotterdam
Erasmus Mc
Arking, Dan E.
United States, Baltimore
Johns Hopkins Medicine
Arnett, Donna K.
United States, Lexington
College of Public Health
Boerwinkle, Eric A.
United States, Houston
University of Texas Health Science Center at Houston
United States, Houston
Baylor College of Medicine
Brody, Jennifer A.
United States, Seattle
University of Washington
Broeckel, Ulrich
United States, Milwaukee
Medical College of Wisconsin
Brumat, Marco
Italy, Trieste
Università Degli Studi Di Trieste
Burke, Gregory L.
United States, Winston Salem
Wake Forest University School of Medicine
Cabrera, Claudia P.
United Kingdom, London
Queen Mary University of London
Canouil, Mickaël
France, Lille
Institut Pasteur de Lille
Chee, Miaoli
Singapore, Singapore City
Singapore National Eye Centre
Chen, Yii Der Ida
United States, Torrance
Harbor-ucla Medical Center
Connell, John M.C.
United Kingdom, Dundee
University of Dundee
de Silva, Hithanadura Janaka
Sri Lanka, Kelaniya
University of Kelaniya
de Vries, Paul S.
United States, Houston
University of Texas Health Science Center at Houston
Eiríksdóttir, Gudný H.
Iceland, Kopavogur
Icelandic Heart Association
Faul, Jessica D.
United States, Ann Arbor
University of Michigan, Ann Arbor
Forrester, Terrence E.
Jamaica, Kingston
The University of the West Indies
Fox, Ervin R.
United States, Jackson
University of Mississippi Medical Center
Friedlander, Yechiel
Israel, Jerusalem
Hebrew University of Jerusalem
Gao, He
United Kingdom, London
Imperial College London
United Kingdom, London
Mrc Centre for Environment and Health
Gigante, Bruna
Sweden, Stockholm
Karolinska Universitetssjukhuset
Sweden, Danderyd
Danderyds Sjukhus
Giulianini, Franco
United States, Boston
Brigham and Women's Hospital
Gu, C. Charles
United States, St. Louis
Washington University School of Medicine in St. Louis
Gu, Dongfeng
China, Beijing
Chinese Academy of Medical Sciences & Peking Union Medical College
Harris, Tamara B.
United States, Bethesda
National Institutes of Health Nih
He, Jiang Y.
United States, New Orleans
Tulane University School of Public Health and Tropical Medicine
United States, New Orleans
Tulane University School of Medicine
Hunt, Steven C.
United States, Salt Lake City
The University of Utah
Qatar, Doha
Weill Cornell Medicine-qatar
Ikram, Mohammad Arfan
Netherlands, Rotterdam
Erasmus Mc
Irvin, Marguerite Ryan
United States, Birmingham
The University of Alabama at Birmingham
Kähönen, Mika A.P.
Finland, Tampere
University Hospital of Tampere
Finland, Tampere
Tampere University
Kavousi, Maryam
Netherlands, Rotterdam
Erasmus Mc
Khor, Chiea Chuen
Singapore, Singapore City
Agency for Science, Technology and Research, Singapore
Singapore, Singapore City
National University of Singapore
Kilpeläinen, Tuomas Oskari
Denmark, Copenhagen
Københavns Universitet
United States, New York
Icahn School of Medicine at Mount Sinai
Koh, Woon Puay
Singapore, Singapore City
National University of Singapore
Singapore, Singapore City
Duke-nus Medical School
Komulainen, Pirjo
Finland, Kuopio
Itä-suomen Yliopisto
Kraja, Aldi T.
United States, St. Louis
Washington University School of Medicine in St. Louis
Krieger, Jose E.
Brazil, Sao Paulo
Universidade de São Paulo
Langefeld, Carl D.
United States, Winston Salem
Wake Forest University School of Medicine
Liang, Jingjing
United States, Cleveland
Case Western Reserve University
Liewald, David C.M.
United Kingdom, Edinburgh
The University of Edinburgh
Liu, Chingti
United States, Boston
School of Public Health
Liu, Jianjun
Singapore, Singapore City
Agency for Science, Technology and Research, Singapore
Singapore, Singapore City
National University of Singapore
Lohman, Kurt K.
United States, Winston Salem
Wake Forest University Health Sciences
Mägi, Reedik
Estonia, Tartu
Tartu Ülikool
McKenzie, Colin A.
Jamaica, Kingston
The University of the West Indies
Meitinger, Thomas A.
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Munich
Technische Universität München
Metspalu, Andres H.
Estonia, Tartu
Tartu Ülikool
Milaneschi, Yuri
Netherlands, Amsterdam
Amsterdam Neuroscience
Milani, Lili
Estonia, Tartu
Tartu Ülikool
Mook-Kanamori, Dennis Owen
Netherlands, Leiden
Leids Universitair Medisch Centrum
Nalls, Mike A.
United States, Bethesda
National Institute on Aging Nia
United States, Glen Echo
Data Tecnica International
Nelson, Christopher P.
United Kingdom, Leicester
University of Leicester
Norris, Jill M.
United States, Aurora
University of Colorado Anschutz Medical Campus
Ogunniyi, Adesola O.
Nigeria, Ibadan
University of Ibadan
Padmanabhan, Sandosh
United Kingdom, Glasgow
College of Medical, Veterinary & Life Sciences
Palmer, Nicholette (Nichole)
United States, Winston Salem
Wake Forest University School of Medicine
Pedersen, Nancy Lee
Sweden, Stockholm
Karolinska Institutet
Perls, Thomas T.
United States, Boston
Boston University Chobanian & Avedisian School of Medicine
Peters, Annette Michael
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Petersmann, Astrid
Germany, Greifswald
Universitätsmedizin Greifswald
Peyser, Patricia A.
United States, Ann Arbor
University of Michigan, Ann Arbor
Polašek, Ozren
Croatia, Split
School of Medicine, University of Split
Croatia, Split
Klinički Bolnički Centar Split
Croatia, Zagreb
Klinika za Psihijatriju Sveti Ivan
Porteous, David John
United Kingdom, Edinburgh
The University of Edinburgh
Raffel, Leslie J.
United States, Irvine
University of California, Irvine
Rotter, Jerome I.
United States, Torrance
Harbor-ucla Medical Center
Rudan, Igor
United Kingdom, Edinburgh
The University of Edinburgh
Salako, Babatunde Lawal
Nigeria, Ibadan
University of Ibadan
Schreiner, Pamela J.
United States, Minneapolis
University of Minnesota Twin Cities
Shikany, James M.
United States, Birmingham
The University of Alabama at Birmingham
Sitlani, Colleen M.
United States, Seattle
University of Washington
Smith, Jennifer Anne
United States, Ann Arbor
University of Michigan, Ann Arbor
Starr, John Michael
United Kingdom, Edinburgh
The University of Edinburgh
Strauch, Konstantin
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Munich
Ludwig-maximilians-universität München
Swertz, Morris A.
Netherlands, Groningen
Rijksuniversiteit Groningen
Teumer, Alexander
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Germany, Greifswald
Universitätsmedizin Greifswald
Uitterlinden, André G.
Netherlands, Rotterdam
Erasmus Mc
Vaidya, Dhananjay M.
United States, Baltimore
Johns Hopkins School of Medicine
Waldenberger, Melanie
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Wang, Lihua
United States, St. Louis
Washington University School of Medicine in St. Louis
Wang, Yaxing
China, Beijing
Beijing Institute of Ophthalmology
Weir, David R.
United States, Ann Arbor
University of Michigan, Ann Arbor
Yao, Jie
United States, Torrance
Harbor-ucla Medical Center
Yu, Bing
United States, Houston
University of Texas Health Science Center at Houston
Yuan, Jianmin
United States, Pittsburgh
University of Pittsburgh
Zhao, Wei
United States, Ann Arbor
University of Michigan, Ann Arbor
Zonderman, Alan B.
United States, Bethesda
National Institutes of Health Nih
Becker, Diane M.
United States, Baltimore
Johns Hopkins School of Medicine
Bowden, Donald W.
United States, Winston Salem
Wake Forest University School of Medicine
Deary, Ian J.
United Kingdom, Edinburgh
The University of Edinburgh
Dörr, Marcus
Germany, Berlin
Deutsches Zentrum Für Herz-kreislauf-forschung E. V.
Germany, Greifswald
Universitätsmedizin Greifswald
Esko, Tönu
Estonia, Tartu
Tartu Ülikool
United States, Cambridge
Harvard University
Freedman, Barry I.
United States, Winston Salem
Wake Forest University School of Medicine
Froguel, Philippe
France, Lille
Institut Pasteur de Lille
United Kingdom, London
Imperial College London
Gasparini, Paolo P.
Italy, Trieste
Università Degli Studi Di Trieste
Italy, Trieste
Irccs Burlo Garofolo
Gieger, Christian
Germany, Oberschleissheim
Helmholtz Center Munich German Research Center for Environmental Health
Germany, Oberschleissheim
Deutsches Zentrum Für Diabetesforschung
Jonas, Jost Bruno
Germany, Heidelberg
Universität Heidelberg
China, Beijing
Capital Medical University
Kato, Norihiro
Japan, Tokyo
National Center for Global Health and Medicine
Lakka, Timo Antero
Finland, Kuopio
Itä-suomen Yliopisto
Finland, Kuopio
Kuopio University Hospital
Leander, Karin
Sweden, Stockholm
Karolinska Institutet
Lehtimäki, Terho J.
Finland, Tampere
Fimlab Laboratoriot oy
Finland, Tampere
Tampere University
Magnusson, Patrik K.E.
Sweden, Stockholm
Karolinska Institutet
Marqués-Vidal, Pedro Manuel
Switzerland, Lausanne
Université de Lausanne Unil
Penninx, Brenda W. J. H.
Netherlands, Amsterdam
Amsterdam Neuroscience
Samani, Nilesh J.
United Kingdom, Leicester
University of Leicester
van der Harst, Pim
Netherlands, Groningen
Rijksuniversiteit Groningen
Netherlands, Utrecht
Netherlands Heart Institute
Wagenknecht, Lynne E.
United States, Winston Salem
Wake Forest University School of Medicine
Wu, Tangchun
China, Wuhan
Huazhong University of Science and Technology
Zheng, Wei
United States, Nashville
Vanderbilt University School of Medicine
Bouchard, Claude E.
United States, Baton Rouge
Pennington Biomedical Research Center
Cooper, Richard S.
United States, Chicago
Loyola University Chicago
Correa, Adolfo
Unknown Affiliation
Evans, Michele Kim
United States, Bethesda
National Institutes of Health Nih
Gudnason, V. G.
Iceland, Kopavogur
Icelandic Heart Association
Iceland, Reykjavik
Haskoli Islands
Hayward, Caroline
United Kingdom, Edinburgh
Mrc Human Genetics Unit
Horta, Bernardo Lessa
Brazil, Pelotas
Universidade Federal de Pelotas
Kritchevsky, Stephen B.
United States, Winston Salem
Wake Forest University School of Medicine
Levy, Daniel A.
United States, Framingham
Framingham Heart Study
United States, Bethesda
National Institutes of Health Nih
Palmas, Walter R.
United States, New York
Columbia University Irving Medical Center
Pereira, Alexandre Da Costa
Brazil, Sao Paulo
Universidade de São Paulo
Province, Michael A.
United States, St. Louis
Washington University School of Medicine in St. Louis
Psaty, Bruce M.
United States, Seattle
University of Washington
United States, Oakland
Kaiser Permanente
Ridker, Paul M.
United States, Boston
Harvard Medical School
United States, Boston
Brigham and Women's Hospital
Rotimi, Charles N.
United States, Bethesda
National Institutes of Health Nih
Tai, E. Shyong
Singapore, Singapore City
National University of Singapore
Singapore, Singapore City
Duke-nus Medical School
van Dam, Robertus Martinus
Singapore, Singapore City
National University of Singapore
van Duijn, Cornelia M.
Netherlands, Rotterdam
Erasmus Mc
United Kingdom, Oxford
University of Oxford
Wong, Tienyin
Singapore, Singapore City
Singapore Eye Research Institute
Singapore, Singapore City
Duke-nus Medical School
Rice, Kenneth Martin
United States, Seattle
University of Washington
Gauderman, William James
United States, Los Angeles
University of Southern California
Morrison, Alanna C.
United States, Houston
University of Texas Health Science Center at Houston
North, Kari E.
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Kardia, Sharon L.R.
United States, Ann Arbor
University of Michigan, Ann Arbor
Caulfield, Mark J.
United Kingdom, London
Queen Mary University of London
Elliott, Paul E.
United Kingdom, London
Imperial College London
United Kingdom, London
Mrc Centre for Environment and Health
Munroe, Patricia B.
United Kingdom, London
Queen Mary University of London
Franks, Paul W.
Sweden, Lund
Skånes Universitetssjukhus
Sweden, Umea
Umeå Universitet
Rao, Dabeeru C.
United States, St. Louis
Washington University School of Medicine in St. Louis
Fornage, Myriam
United States, Houston
University of Texas Health Science Center at Houston
Statistics
Citations: 13
Authors: 194
Affiliations: 112
Identifiers
Doi:
10.1038/s41380-020-0719-3
ISSN:
13594184
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cohort Study
Study Approach
Systematic review