Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Lisa de las Fuentes^{1

2}, Yun Ju Sung³, Raymond Noordam⁴, Thomas Winkler⁵, Mary F Feitosa⁶, Karen Schwander⁷, Amy R Bentley⁸, Michael R Brown⁹, Xiuqing Guo¹⁰, Alisa Manning^{11

12}, Daniel I Chasman^{13

14}, Hugues Aschard^{15

16}, Traci M Bartz¹⁷, Lawrence F Bielak¹⁸, Archie Campbell¹⁹, Ching-Yu Cheng^{20

21}, Rajkumar Dorajoo²², Fernando P Hartwig^{23

24}, A R V R Horimoto²⁵, Changwei Li²⁶, Ruifang Li-Gao²⁷, Yongmei Liu²⁸, Jonathan Marten²⁹, Solomon K Musani³⁰, Ioanna Ntalla³¹, Tuomo Rankinen³², Melissa Richard³³, Xueling Sim³⁴, Albert V Smith^{35

36}, Salman M Tajuddin³⁷, Bamidele O Tayo³⁸, Dina Vojinovic³⁹, Helen R Warren^{31

40}, Deng Xuan⁴¹, Maris Alver^{42

43}, Mathilde Boissel⁴⁴, Jin-Fang Chai³⁴, Xu Chen⁴⁵, Kaare Christensen⁴⁶, Jasmin Divers⁴⁷, Evangelos Evangelou^{48

49}, Chuan Gao⁵⁰, Giorgia Girotto^{51

52}, Sarah E Harris⁵³, Meian He⁵⁴, Fang-Chi Hsu⁴⁷, Brigitte Kühnel^{55

56}, Federica Laguzzi⁵⁷, Xiaoyin Li^{58

59}, Leo-Pekka Lyytikäinen^{60

61}, Ilja M Nolte⁶², Alaitz Poveda⁶³, Rainer Rauramaa⁶⁴, Muhammad Riaz⁶⁵, Rico Rueedi^{66

67}, Xiao-Ou Shu⁶⁸, Harold Snieder⁶², Tamar Sofer⁶⁹, Fumihiko Takeuchi⁷⁰, Niek Verweij⁷¹, Erin B Ware⁷², Stefan Weiss^{73

74}, Lisa R Yanek⁷⁵, Najaf Amin³⁹, Dan E Arking⁷⁶, Donna K Arnett⁷⁷, Sven Bergmann^{66

67}, Eric Boerwinkle^{9

78}, Jennifer A Brody⁷⁹, Ulrich Broeckel⁸⁰, Marco Brumat⁵¹, Gregory Burke⁸¹, Claudia P Cabrera^{31

40}, Mickaël Canouil⁴⁴, Miao Li Chee⁸², Yii-Der Ida Chen¹⁰, Massimiliano Cocca⁵², John Connell⁸³, H Janaka de Silva⁸⁴, Paul S de Vries⁹, Gudny Eiriksdottir³⁶, Jessica D Faul⁷², Virginia Fisher⁴¹, Terrence Forrester⁸⁵, Ervin F Fox⁸⁶, Yechiel Friedlander⁸⁷, He Gao^{48

88}, Bruna Gigante^{89

90}, Franco Giulianini⁹¹, Chi Charles Gu⁷, Dongfeng Gu⁹², Tamara B Harris⁹³, Jiang He^{94

95}, Sami Heikkinen^{96

97}, Chew-Kiat Heng^{98

99}, Steven Hunt^{100

101}, M Arfan Ikram^{39

102}, Marguerite R Irvin¹⁰³, Mika Kähönen^{104

105}, Maryam Kavousi³⁹, Chiea Chuen Khor^{22

106}, Tuomas O Kilpeläinen^{107

108}, Woon-Puay Koh^{34

109}, Pirjo Komulainen⁶⁴, Aldi T Kraja⁶, J E Krieger²⁵, Carl D Langefeld⁴⁷, Yize Li⁷, Jingjing Liang⁵⁸, David C M Liewald⁵³, Ching-Ti Liu⁴¹, Jianjun Liu^{22

34}, Kurt K Lohman¹¹⁰, Reedik Mägi⁴², Colin A McKenzie⁸⁵, Thomas Meitinger^{111

112}, Andres Metspalu^{42

43}, Yuri Milaneschi¹¹³, Lili Milani⁴², Dennis O Mook-Kanamori^{27

114}, Mike A Nalls^{115

116}, Christopher P Nelson^{117

118}, Jill M Norris¹¹⁹, Jeff O'Connell^{120

121}, Adesola Ogunniyi¹²², Sandosh Padmanabhan¹²³, Nicholette D Palmer¹²⁴, Nancy L Pedersen⁴⁵, Thomas Perls¹²⁵, Annette Peters^{56

126}, Astrid Petersmann¹²⁷, Patricia A Peyser¹⁸, Ozren Polasek^{128

129

130}, David J Porteous^{19

53}, Leslie J Raffel¹³¹, Treva K Rice⁷, Jerome I Rotter¹⁰, Igor Rudan¹³², Oscar-Leonel Rueda-Ochoa³⁹, Charumathi Sabanayagam^{20

21}, Babatunde L Salako¹²², Pamela J Schreiner¹³³, James M Shikany¹³⁴, Stephen S Sidney¹³⁵, Mario Sims³⁰, Colleen M Sitlani⁷⁹, Jennifer A Smith^{18

72}, John M Starr^{136

137}, Konstantin Strauch^{138

139}, Morris A Swertz¹⁴⁰, Alexander Teumer^{74

141}, Yih Chung Tham²⁰, André G Uitterlinden^{39

142}, Dhananjay Vaidya⁷⁵, M Yldau van der Ende⁷¹, Melanie Waldenberger^{55

56

126}, Lihua Wang⁶, Ya-Xing Wang¹⁴³, Wen-Bin Wei¹⁴⁴, David R Weir⁷², Wanqing Wen⁶⁸, Jie Yao¹⁰, Bing Yu⁹, Caizheng Yu⁵⁴, Jian-Min Yuan^{145

146}, Wei Zhao¹⁸, Alan B Zonderman¹⁴⁷, Diane M Becker⁷⁵, Donald W Bowden¹²⁴, Ian J Deary⁵³, Marcus Dörr^{74

148}, Tõnu Esko^{42

149}, Barry I Freedman¹⁵⁰, Philippe Froguel^{44

151}, Paolo Gasparini^{51

52}, Christian Gieger^{55

152}, Jost Bruno Jonas^{153

154}, Candace M Kammerer¹⁵⁵, Norihiro Kato⁷⁰, Timo A Lakka^{64

96

156}, Karin Leander⁵⁷, Terho Lehtimäki^{60

61}; Lifelines Cohort Study; Patrik K E Magnusson⁴⁵, Pedro Marques-Vidal¹⁵⁷, Brenda W J H Penninx¹¹³, Nilesh J Samani^{117

118}, Pim van der Harst^{71

158}, Lynne E Wagenknecht⁸¹, Tangchun Wu⁵⁴, Wei Zheng⁶⁸, Xiaofeng Zhu⁵⁸, Claude Bouchard³², Richard S Cooper³⁸, Adolfo Correa³⁰, Michele K Evans³⁷, Vilmundur Gudnason^{36

159}, Caroline Hayward²⁹, Bernardo L Horta²³, Tanika N Kelly⁹⁴, Stephen B Kritchevsky¹⁶⁰, Daniel Levy^{161

162}, Walter R Palmas¹⁶³, A C Pereira²⁵, Michael M Province⁶, Bruce M Psaty^{164

165}, Paul M Ridker^{14

91}, Charles N Rotimi⁸, E Shyong Tai^{34

109

166}, Rob M van Dam^{34

166}, Cornelia M van Duijn^{39

167}, Tien Yin Wong^{20

21}, Kenneth Rice¹⁶⁸, W James Gauderman¹⁶⁹, Alanna C Morrison⁹, Kari E North¹⁷⁰, Sharon L R Kardia¹⁸, Mark J Caulfield^{31

40}, Paul Elliott^{48

88}, Patricia B Munroe^{31

40}, Paul W Franks^{63

171}, Dabeeru C Rao⁷, Myriam Fornage³³

Affiliations

¹ Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, 63110, USA. lfuentes@wustl.edu.
² Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA. lfuentes@wustl.edu.
³ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA. yunju@wustl.edu.
⁴ Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2333ZA, The Netherlands.
⁵ Department of Genetic Epidemiology, University of Regensburg, 93051, Regensburg, Germany.
⁶ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63108, USA.
⁷ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁸ Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
⁹ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
¹⁰ The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹¹ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
¹² Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
¹³ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
¹⁴ Harvard Medical School, Boston, MA, 02115, USA.
¹⁵ Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
¹⁶ Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, 75724, France.
¹⁷ Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, WA, 98101, USA.
¹⁸ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁹ Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁰ Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Ecy Centre, Singapore, 169856, Singapore.
²¹ Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore.
²² Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138672, Singapore.
²³ Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, RS, 96020-220, Brazil.
²⁴ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, UK.
²⁵ Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, 5403000, Brazil.
²⁶ Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, Athens, GA, 30602, USA.
²⁷ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333ZA, Netherlands.
²⁸ Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, NC, 27157, USA.
²⁹ Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
³⁰ Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39213, USA.
³¹ Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
³² Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
³³ Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 70808, USA.
³⁴ Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
³⁵ Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
³⁶ Icelandic Heart Association, Kopavogur, 201, Iceland.
³⁷ Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
³⁸ Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, 60153, USA.
³⁹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴⁰ NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, London, EC1M 6BQ, UK.
⁴¹ Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
⁴² Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia.
⁴³ Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, 51010, Estonia.
⁴⁴ CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
⁴⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
⁴⁶ Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, Southern Denmark University, Odense, 5000, Denmark.
⁴⁷ Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
⁴⁸ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁴⁹ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
⁵⁰ Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
⁵¹ Medical Genetics, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, 34100, Italy.
⁵² Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34100, Italy.
⁵³ Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁵⁴ Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
⁵⁵ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
⁵⁶ Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
⁵⁷ Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17177, Sweden.
⁵⁸ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
⁵⁹ Department of Mathematics and Statistics, University of Minnesota, Duluth, MN, 55812, USA.
⁶⁰ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland.
⁶¹ Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, 33014, Finland.
⁶² University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, 9700RB, The Netherlands.
⁶³ Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Skåne, 205 02, Sweden.
⁶⁴ Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
⁶⁵ College of Medicine, Biological Sciences and Psychology, Health Sciences, The Infant Mortality and Morbidity Studies (TIMMS), Leicester, LE1 7RH, UK.
⁶⁶ Department of Computational Biology, University of Lausanne, Lausanne, 1011, Switzerland.
⁶⁷ Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
⁶⁸ Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37203, USA.
⁶⁹ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, 02115, USA.
⁷⁰ Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 1628655, Japan.
⁷¹ University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9700, The Netherlands.
⁷² Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
⁷³ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 9713GZ, Greifswald, Germany.
⁷⁴ DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, 17475, Greifswald, Germany.
⁷⁵ Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁷⁶ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
⁷⁷ Dean's Office, University of Kentucky College of Public Health, Lexington, KY, 40536, USA.
⁷⁸ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
⁷⁹ Cardiovascular Health Research Unit, Medicine, University of Washington, Seattle, WA, 98101, USA.
⁸⁰ Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
⁸¹ Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA.
⁸² Statistics Unit, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
⁸³ Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY, UK.
⁸⁴ Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
⁸⁵ Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, JMAAW15, Jamaica.
⁸⁶ Cardiology, Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
⁸⁷ Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, 91120, Israel.
⁸⁸ MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG, UK.
⁸⁹ Cardiovascular Unit, Bioclinicum, Department of Medicine, Karolinska Hospital, Stockholm, 17164, Sweden.
⁹⁰ Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Stockholm, 18288, Sweden.
⁹¹ Brigham and Women's Hospital, Boston, MA, 02215, USA.
⁹² Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁹³ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
⁹⁴ Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA.
⁹⁵ Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
⁹⁶ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Kuopio, 70211, Finland.
⁹⁷ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70211, Finland.
⁹⁸ Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
⁹⁹ Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore, 119228, Singapore.
¹⁰⁰ Cardiovascular Genetics, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84108, USA.
¹⁰¹ Weill Cornell Medicine in Qatar, Doha, Qatar.
¹⁰² Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁰³ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
¹⁰⁴ Department of Clinical Physiology, Tampere University Hospital, Tampere, 33521, Finland.
¹⁰⁵ Department of Clinical Physiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, 33014, Finland.
¹⁰⁶ Department of Biochemistry, National University of Singapore, Singapore, 117596, Singapore.
¹⁰⁷ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark.
¹⁰⁸ Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
¹⁰⁹ Health Services and Systems Research, Duke-NUS Medical School, Singapore, 169857, Singapore.
¹¹⁰ Public Health Sciences, Biostatistics and Data Science, Wake Forest University Health Sciences, Winston-Salem, NC, 27157, USA.
¹¹¹ Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
¹¹² Institute of Human Genetics, Technische Universität München, 80333, Munich, Germany.
¹¹³ Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, 1081 BT, The Netherlands.
¹¹⁴ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333ZA, Netherlands.
¹¹⁵ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20895, USA.
¹¹⁶ Data Tecnica International, Glen Echo, MD, 20812, USA.
¹¹⁷ Department of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9QP, UK.
¹¹⁸ NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK.
¹¹⁹ Department of Epidemiology, University of Colorado Denver, Aurora, CO, 80045, USA.
¹²⁰ Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
¹²¹ Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
¹²² Department of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
¹²³ British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
¹²⁴ Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
¹²⁵ Department of Medicine, Geriatrics Section, Boston Medical Center, Boston University School of Medicine, Boston, MA, 02118, USA.
¹²⁶ DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 85764, Neuherberg, Germany.
¹²⁷ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
¹²⁸ University of Split School of Medicine, Split, Croatia.
¹²⁹ University Hospital Split, Split, Croatia.
¹³⁰ Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia.
¹³¹ Division of Genetic and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, 92868, USA.
¹³² Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
¹³³ Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
¹³⁴ Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 25249, USA.
¹³⁵ Division of Research, Kaiser Permanente of Northern California, Oakland, CA, USA.
¹³⁶ Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, EH8 9AZ, UK.
¹³⁷ Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK.
¹³⁸ Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
¹³⁹ Institute of Medical Informatics Biometry and Epidemiology, Ludwig-Maximilians-Universitat Munchen, 80539, Munich, Germany.
¹⁴⁰ University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, 9700RB, The Netherlands.
¹⁴¹ Institute for Community Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
¹⁴² Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁴³ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.
¹⁴⁴ Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.
¹⁴⁵ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
¹⁴⁶ Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, , University of Pittsburgh, Pittsburgh, PA, 15232, USA.
¹⁴⁷ Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
¹⁴⁸ Department of Internal Medicine B, University Medicine Greifswald, 17475, Greifswald, Germany.
¹⁴⁹ Broad Institute of the Massachusetts Institute of Technology and Harvard University, Boston, MA, 02142, USA.
¹⁵⁰ Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-, Salem, NC, 27157, USA.
¹⁵¹ Department of Genomics of Common Disease, Imperial College London, London, W12 0NN, UK.
¹⁵² German Center for Diabetes Research (DZD e.V.), 85764, Neuherberg, Germany.
¹⁵³ Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, 68167, Mannheim, Germany.
¹⁵⁴ Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Capital Medical University, 100730, Beijing, China.
¹⁵⁵ Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
¹⁵⁶ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70211, Finland.
¹⁵⁷ Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, 1011, Switzerland.
¹⁵⁸ Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Ultrecht, The Netherlands.
¹⁵⁹ Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
¹⁶⁰ Sticht Center for Health Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
¹⁶¹ NHLBI Framingham Heart Study, Framingham, MA, 01702, USA.
¹⁶² Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, 20892, USA.
¹⁶³ Division of General Medicine, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
¹⁶⁴ Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, 98101, USA.
¹⁶⁵ Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
¹⁶⁶ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
¹⁶⁷ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹⁶⁸ Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
¹⁶⁹ Biostatistics, Preventive Medicine, University of Southern California, Los Angeles, CA, 90032, USA.
¹⁷⁰ Epidemiology, University of North Carolina Gilling School of Global Public Health, Chapel Hill, NC, 27514, USA.
¹⁷¹ Department of Public Health & Clinical Medicine, Umeå University, Umeå, Västerbotten, 901 85, Sweden.

PMID: 32372009
PMCID: PMC7641978
DOI: 10.1038/s41380-020-0719-3

Meta-Analysis

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Lisa de las Fuentes et al. Mol Psychiatry. 2021 Jun.

. 2021 Jun;26(6):2111-2125.

doi: 10.1038/s41380-020-0719-3. Epub 2020 May 5.

Authors

Affiliations

¹ Cardiovascular Division, Department of Medicine, Washington University, St. Louis, MO, 63110, USA. lfuentes@wustl.edu.
² Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA. lfuentes@wustl.edu.
³ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA. yunju@wustl.edu.
⁴ Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, 2333ZA, The Netherlands.
⁵ Department of Genetic Epidemiology, University of Regensburg, 93051, Regensburg, Germany.
⁶ Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, St. Louis, MO, 63108, USA.
⁷ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁸ Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
⁹ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
¹⁰ The Institute for Translational Genomics and Population Sciences, Division of Genomic Outcomes, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, 90502, USA.
¹¹ Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, MA, 02114, USA.
¹² Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.
¹³ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
¹⁴ Harvard Medical School, Boston, MA, 02115, USA.
¹⁵ Department of Epidemiology, Harvard School of Public Health, Boston, MA, 02115, USA.
¹⁶ Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, Paris, 75724, France.
¹⁷ Cardiovascular Health Research Unit, Biostatistics and Medicine, University of Washington, Seattle, WA, 98101, USA.
¹⁸ Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, 48109, USA.
¹⁹ Centre for Genomic & Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
²⁰ Ocular Epidemiology, Singapore Eye Research Institute, Singapore National Ecy Centre, Singapore, 169856, Singapore.
²¹ Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, 169857, Singapore.
²² Genome Institute of Singapore, Agency for Science Technology and Research, Singapore, 138672, Singapore.
²³ Postgraduate Programme in Epidemiology, Federal University of Pelotas, Pelotas, RS, 96020-220, Brazil.
²⁴ Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, BS8 2BN, UK.
²⁵ Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, 5403000, Brazil.
²⁶ Epidemiology and Biostatistics, University of Georgia at Athens College of Public Health, Athens, GA, 30602, USA.
²⁷ Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, 2333ZA, Netherlands.
²⁸ Public Health Sciences, Epidemiology and Prevention, Wake Forest University Health Sciences, Winston-Salem, NC, 27157, USA.
²⁹ Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK.
³⁰ Jackson Heart Study, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, 39213, USA.
³¹ Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, UK.
³² Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
³³ Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, 70808, USA.
³⁴ Saw Swee Hock School of Public Health, National University Health System and National University of Singapore, Singapore, 117549, Singapore.
³⁵ Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.
³⁶ Icelandic Heart Association, Kopavogur, 201, Iceland.
³⁷ Health Disparities Research Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
³⁸ Department of Public Health Sciences, Loyola University Chicago, Maywood, IL, 60153, USA.
³⁹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁴⁰ NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, London, EC1M 6BQ, UK.
⁴¹ Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
⁴² Estonian Genome Center, Institute of Genomics, University of Tartu, Tartu, 51010, Estonia.
⁴³ Department of Biotechnology, Institute of Molecular and Cell Biology, University of Tartu, Tartu, 51010, Estonia.
⁴⁴ CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, 59000, France.
⁴⁵ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Stockholm, 17177, Sweden.
⁴⁶ Unit of Epidemiology, Biostatistics and Biodemography, Department of Public Health, Southern Denmark University, Odense, 5000, Denmark.
⁴⁷ Biostatistical Sciences, Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
⁴⁸ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, W2 1PG, UK.
⁴⁹ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, 45110, Greece.
⁵⁰ Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
⁵¹ Medical Genetics, Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, 34100, Italy.
⁵² Institute for Maternal and Child Health-IRCCS "Burlo Garofolo", Trieste, 34100, Italy.
⁵³ Department of Psychology, Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁵⁴ Department of Occupational and Environmental Health and State Key Laboratory of Environmental Health for Incubating, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
⁵⁵ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
⁵⁶ Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
⁵⁷ Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, 17177, Sweden.
⁵⁸ Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, 44106, USA.
⁵⁹ Department of Mathematics and Statistics, University of Minnesota, Duluth, MN, 55812, USA.
⁶⁰ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, 33520, Finland.
⁶¹ Department of Clinical Chemistry, Finnish Cardiovascular Research Center - Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, 33014, Finland.
⁶² University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, 9700RB, The Netherlands.
⁶³ Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Skåne University Hospital, Malmö, Skåne, 205 02, Sweden.
⁶⁴ Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, 70100, Finland.
⁶⁵ College of Medicine, Biological Sciences and Psychology, Health Sciences, The Infant Mortality and Morbidity Studies (TIMMS), Leicester, LE1 7RH, UK.
⁶⁶ Department of Computational Biology, University of Lausanne, Lausanne, 1011, Switzerland.
⁶⁷ Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland.
⁶⁸ Division of Epidemiology, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37203, USA.
⁶⁹ Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA, 02115, USA.
⁷⁰ Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, 1628655, Japan.
⁷¹ University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, 9700, The Netherlands.
⁷² Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, 48104, USA.
⁷³ Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, 9713GZ, Greifswald, Germany.
⁷⁴ DZHK (German Centre for Cardiovascular Health), Partner Site Greifswald, 17475, Greifswald, Germany.
⁷⁵ Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
⁷⁶ McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
⁷⁷ Dean's Office, University of Kentucky College of Public Health, Lexington, KY, 40536, USA.
⁷⁸ Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, 77030, USA.
⁷⁹ Cardiovascular Health Research Unit, Medicine, University of Washington, Seattle, WA, 98101, USA.
⁸⁰ Section of Genomic Pediatrics, Department of Pediatrics, Medicine and Physiology, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
⁸¹ Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, 27109, USA.
⁸² Statistics Unit, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore.
⁸³ Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, DD1 9SY, UK.
⁸⁴ Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
⁸⁵ Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, JMAAW15, Jamaica.
⁸⁶ Cardiology, Medicine, University of Mississippi Medical Center, Jackson, MS, 39216, USA.
⁸⁷ Braun School of Public Health, Hebrew University-Hadassah Medical Center, Jerusalem, 91120, Israel.
⁸⁸ MRC-PHE Centre for Environment and Health, Imperial College London, London, W2 1PG, UK.
⁸⁹ Cardiovascular Unit, Bioclinicum, Department of Medicine, Karolinska Hospital, Stockholm, 17164, Sweden.
⁹⁰ Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd University Hospital, Stockholm, 18288, Sweden.
⁹¹ Brigham and Women's Hospital, Boston, MA, 02215, USA.
⁹² Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
⁹³ Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Bethesda, MD, 20892, USA.
⁹⁴ Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, 70112, USA.
⁹⁵ Medicine, Tulane University School of Medicine, New Orleans, LA, 70112, USA.
⁹⁶ Institute of Biomedicine, School of Medicine, University of Eastern Finland, Kuopio Campus, Kuopio, 70211, Finland.
⁹⁷ Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, 70211, Finland.
⁹⁸ Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
⁹⁹ Khoo Teck Puat - National University Children's Medical Institute, National University Health System, Singapore, 119228, Singapore.
¹⁰⁰ Cardiovascular Genetics, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 84108, USA.
¹⁰¹ Weill Cornell Medicine in Qatar, Doha, Qatar.
¹⁰² Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁰³ Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
¹⁰⁴ Department of Clinical Physiology, Tampere University Hospital, Tampere, 33521, Finland.
¹⁰⁵ Department of Clinical Physiology, Finnish Cardiovascular Research Center-Tampere, Faculty of Medicine and Health Technology, University of Tampere, Tampere, 33014, Finland.
¹⁰⁶ Department of Biochemistry, National University of Singapore, Singapore, 117596, Singapore.
¹⁰⁷ Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DK-2200, Denmark.
¹⁰⁸ Department of Environmental Medicine and Public Health, The Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.
¹⁰⁹ Health Services and Systems Research, Duke-NUS Medical School, Singapore, 169857, Singapore.
¹¹⁰ Public Health Sciences, Biostatistics and Data Science, Wake Forest University Health Sciences, Winston-Salem, NC, 27157, USA.
¹¹¹ Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
¹¹² Institute of Human Genetics, Technische Universität München, 80333, Munich, Germany.
¹¹³ Department of Psychiatry, Amsterdam Neuroscience and Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, 1081 BT, The Netherlands.
¹¹⁴ Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, 2333ZA, Netherlands.
¹¹⁵ Molecular Genetics Section, Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20895, USA.
¹¹⁶ Data Tecnica International, Glen Echo, MD, 20812, USA.
¹¹⁷ Department of Cardiovascular Sciences, University of Leicester, Leicester, LE3 9QP, UK.
¹¹⁸ NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, LE3 9QP, UK.
¹¹⁹ Department of Epidemiology, University of Colorado Denver, Aurora, CO, 80045, USA.
¹²⁰ Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, MD, USA.
¹²¹ Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
¹²² Department of Medicine, University of Ibadan, Ibadan, Oyo, Nigeria.
¹²³ British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.
¹²⁴ Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
¹²⁵ Department of Medicine, Geriatrics Section, Boston Medical Center, Boston University School of Medicine, Boston, MA, 02118, USA.
¹²⁶ DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, 85764, Neuherberg, Germany.
¹²⁷ Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
¹²⁸ University of Split School of Medicine, Split, Croatia.
¹²⁹ University Hospital Split, Split, Croatia.
¹³⁰ Psychiatric Hospital "Sveti Ivan", Zagreb, Croatia.
¹³¹ Division of Genetic and Genomic Medicine, Department of Pediatrics, University of California, Irvine, CA, 92868, USA.
¹³² Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, EH8 9AG, UK.
¹³³ Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
¹³⁴ Division of Preventive Medicine, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, 25249, USA.
¹³⁵ Division of Research, Kaiser Permanente of Northern California, Oakland, CA, USA.
¹³⁶ Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, EH8 9AZ, UK.
¹³⁷ Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK.
¹³⁸ Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Germany.
¹³⁹ Institute of Medical Informatics Biometry and Epidemiology, Ludwig-Maximilians-Universitat Munchen, 80539, Munich, Germany.
¹⁴⁰ University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, 9700RB, The Netherlands.
¹⁴¹ Institute for Community Medicine, University Medicine Greifswald, 17475, Greifswald, Germany.
¹⁴² Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.
¹⁴³ Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.
¹⁴⁴ Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, 100730, Beijing, China.
¹⁴⁵ Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
¹⁴⁶ Division of Cancer Control and Population Sciences, UPMC Hillman Cancer, , University of Pittsburgh, Pittsburgh, PA, 15232, USA.
¹⁴⁷ Behavioral Epidemiology Section, Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
¹⁴⁸ Department of Internal Medicine B, University Medicine Greifswald, 17475, Greifswald, Germany.
¹⁴⁹ Broad Institute of the Massachusetts Institute of Technology and Harvard University, Boston, MA, 02142, USA.
¹⁵⁰ Section on Nephrology, Department of Internal Medicine, Wake Forest School of Medicine, Winston-, Salem, NC, 27157, USA.
¹⁵¹ Department of Genomics of Common Disease, Imperial College London, London, W12 0NN, UK.
¹⁵² German Center for Diabetes Research (DZD e.V.), 85764, Neuherberg, Germany.
¹⁵³ Department of Ophthalmology, Medical Faculty Mannheim, University Heidelberg, 68167, Mannheim, Germany.
¹⁵⁴ Beijing Institute of Ophthalmology, Beijing Ophthalmology and Visual Science Key Lab, Beijing Tongren Eye Center, Capital Medical University, 100730, Beijing, China.
¹⁵⁵ Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
¹⁵⁶ Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, 70211, Finland.
¹⁵⁷ Department of Medicine, Internal Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, 1011, Switzerland.
¹⁵⁸ Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Ultrecht, The Netherlands.
¹⁵⁹ Faculty of Medicine, University of Iceland, Reykjavik, 101, Iceland.
¹⁶⁰ Sticht Center for Health Aging and Alzheimer's Prevention, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, 27157, USA.
¹⁶¹ NHLBI Framingham Heart Study, Framingham, MA, 01702, USA.
¹⁶² Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, 20892, USA.
¹⁶³ Division of General Medicine, Department of Medicine, Columbia University Medical Center, New York, NY, 10032, USA.
¹⁶⁴ Cardiovascular Health Research Unit, Epidemiology, Medicine and Health Services, University of Washington, Seattle, WA, 98101, USA.
¹⁶⁵ Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
¹⁶⁶ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119228, Singapore.
¹⁶⁷ Nuffield Department of Population Health, University of Oxford, Oxford, UK.
¹⁶⁸ Department of Biostatistics, University of Washington, Seattle, WA, 98195, USA.
¹⁶⁹ Biostatistics, Preventive Medicine, University of Southern California, Los Angeles, CA, 90032, USA.
¹⁷⁰ Epidemiology, University of North Carolina Gilling School of Global Public Health, Chapel Hill, NC, 27514, USA.
¹⁷¹ Department of Public Health & Clinical Medicine, Umeå University, Umeå, Västerbotten, 901 85, Sweden.

PMID: 32372009
PMCID: PMC7641978
DOI: 10.1038/s41380-020-0719-3

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

The authors declare no conflict of interests.

Figures

**Figure 1.**
Study design with summary of data included in this study. Educ: education status (considering either SomeCol or GradCol status separately); PC: principal component; EUR: European; AFR: African; ASN: Asian; HIS: Hispanic; BRZ: Brazilian; SNV: single nucleotide variant; TRANS; trans-ancestry (i.e., combining all ancestry groups through meta-analysis).

**Figure 2:. LocusZoom plots for 2 BP loci related to CNS-adrenal signaling**
**(A)** MAP-associated locus adjacent to *ZDHHC17*, identified in AFR and in trans-ancestry, shows roles in CNS-adrenal signaling. In neurons, *ZDHHC17* encodes a membrane protein that mediates fusion of synaptic vesicles to the plasma membrane, enabling the release of neurotransmitters. Murine *zdhhc17* knockout models show impaired hippocampal memory and reduced synaptic plasticity, providing potential biological links to working memory and subsequent educational attainment. **(B)**A locus intragenic to *CADPS*, identified in AFR, is of potential biologic relevance given this gene’s expression in CNS tissue and role in regulating the fusion of neuroendocrine vesicles and release of vasoactive catecholamines from both adrenal and neural tissue. Three LD SNVs have CADD scores >10, and four LD SNVs have ChromHMM state signals consistent with strong evidence of transcription regulation. SBP, systolic blood pressure; DBP, diastolic blood pressure; MAP, mean arterial pressure; PP, pulse pressure. The plots were created using LocusZoom (http://locuszoom.sph.umich.edu/).

See this image and copyright information in PMC

References

1. Kaplan GA, Keil JE. Socioeconomic factors and cardiovascular disease: a review of the literature. Circulation 1993; 88(4 Pt 1): 1973–1998. - PubMed
1. Liberatos P, Link BG, Kelsey JL. The measurement of social class in epidemiology. Epidemiol Rev 1988; 10: 87–121. - PubMed
1. Leng B, Jin Y, Li G, Chen L, Jin N. Socioeconomic status and hypertension: a meta-analysis. J Hypertens 2015; 33(2): 221–229. - PubMed
1. Winkleby MA, Jatulis DE, Frank E, Fortmann SP. Socioeconomic status and health: how education, income, and occupation contribute to risk factors for cardiovascular disease. Am J Public Health 1992; 82(6): 816–820. - PMC - PubMed
1. Basson J, Sung YJ, Schwander K, Kume R, Simino J, de las Fuentes L et al.Gene-education interactions identify novel blood pressure loci in the Framingham Heart Study. Am J Hypertens 2014; 27(3): 431–444. - PMC - PubMed

Publication types

Actions
Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Health Information
Miscellaneous
- NCI CPTAC Assay Portal

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Affiliations

Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Miscellaneous