Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

Louise V Wain¹, Ahmad Vaez^{2

3}, Rick Jansen⁴, Roby Joehanes^{5

6}, Peter J van der Most⁷, A Mesut Erzurumluoglu¹, Paul F O'Reilly⁸, Claudia P Cabrera^{9

10}, Helen R Warren^{9

10}, Lynda M Rose¹¹, Germaine C Verwoert¹², Jouke-Jan Hottenga¹³, Rona J Strawbridge^{14

15}, Tonu Esko^{16

17

18}, Dan E Arking¹⁹, Shih-Jen Hwang^{20

21}, Xiuqing Guo²², Zoltan Kutalik^{23

24}, Stella Trompet²⁵, Nick Shrine¹, Alexander Teumer^{26

27}, Janina S Ried²⁸, Joshua C Bis²⁹, Albert V Smith^{30

31}, Najaf Amin³², Ilja M Nolte², Leo-Pekka Lyytikäinen^{33

34}, Anubha Mahajan³⁵, Nicholas J Wareham³⁶, Edith Hofer^{37

38}, Peter K Joshi³⁹, Kati Kristiansson⁴⁰, Michela Traglia⁴¹, Aki S Havulinna⁴⁰, Anuj Goel⁴², Mike A Nalls^{43

44}, Siim Sõber⁴⁵, Dragana Vuckovic^{46

47}, Jian'an Luan³⁶, Fabiola Del Greco M⁴⁸, Kristin L Ayers⁴⁹, Jaume Marrugat⁵⁰, Daniela Ruggiero⁵¹, Lorna M Lopez^{52

53

54}, Teemu Niiranen⁴⁰, Stefan Enroth⁵⁵, Anne U Jackson⁵⁶, Christopher P Nelson^{7

57}, Jennifer E Huffman⁵⁸, Weihua Zhang^{59

60}, Jonathan Marten⁵⁸, Ilaria Gandin⁴⁷, Sarah E Harris^{52

61}, Tatijana Zemunik⁶², Yingchang Lu⁶³, Evangelos Evangelou^{59

64}, Nabi Shah^{65

66}, Martin H de Borst⁶⁷, Massimo Mangino^{68

69}, Bram P Prins⁷⁰, Archie Campbell^{71

72}, Ruifang Li-Gao⁷³, Ganesh Chauhan^{74

75}, Christopher Oldmeadow⁷⁶, Gonçalo Abecasis⁷⁷, Maryam Abedi⁷⁸, Caterina M Barbieri⁴¹, Michael R Barnes^{9

10}, Chiara Batini¹, John Beilby^{79

80

81}; BIOS Consortium; Tineka Blake¹, Michael Boehnke⁵⁶, Erwin P Bottinger⁶³, Peter S Braund^{7

57}, Morris Brown^{9

10}, Marco Brumat⁴⁷, Harry Campbell³⁹, John C Chambers^{59

60

82}, Massimiliano Cocca⁴⁷, Francis Collins⁸³, John Connell⁸⁴, Heather J Cordell⁸⁵, Jeffrey J Damman¹¹, Gail Davies^{52

86}, Eco J de Geus¹³, Renée de Mutsert⁷³, Joris Deelen⁸⁷, Yusuf Demirkale⁸⁸, Alex S F Doney⁶⁵, Marcus Dörr^{89

27}, Martin Farrall^{35

42}, Teresa Ferreira³⁵, Mattias Frånberg^{14

15

90}, He Gao⁵⁹, Vilmantas Giedraitis⁹¹, Christian Gieger⁹², Franco Giulianini¹¹, Alan J Gow^{52

93}, Anders Hamsten^{14

15}, Tamara B Harris⁹⁴, Albert Hofman^{12

95}, Elizabeth G Holliday⁷⁶, Jennie Hui^{79

80

81

96}, Marjo-Riitta Jarvelin^{97

98

99

100}, Åsa Johansson⁵⁵, Andrew D Johnson^{6

101}, Pekka Jousilahti⁴⁰, Antti Jula⁴⁰, Mika Kähönen^{102

103}, Sekar Kathiresan^{104

105

106}, Kay-Tee Khaw¹⁰⁷, Ivana Kolcic¹⁰⁸, Seppo Koskinen⁴⁰, Claudia Langenberg³⁶, Marty Larson⁶, Lenore J Launer⁹⁴, Benjamin Lehne⁵⁹, David C M Liewald^{52

86}, Li Lin¹⁰⁹, Lars Lind¹¹⁰, François Mach¹⁰⁹, Chrysovalanto Mamasoula¹¹¹, Cristina Menni⁶⁸, Borbala Mifsud⁹, Yuri Milaneschi¹¹², Anna Morgan⁴⁷, Andrew D Morris¹¹³, Alanna C Morrison¹¹⁴, Peter J Munson⁸⁸, Priyanka Nandakumar¹⁹, Quang Tri Nguyen⁸³, Teresa Nutile⁵¹, Albertine J Oldehinkel¹¹⁵, Ben A Oostra³², Elin Org¹⁶, Sandosh Padmanabhan^{72

116}, Aarno Palotie¹¹⁷, Guillaume Paré¹¹⁸, Alison Pattie⁸⁶, Brenda W J H Penninx¹¹², Neil Poulter¹¹⁹, Peter P Pramstaller^{48

120

121}, Olli T Raitakari^{122

123}, Meixia Ren^{9

124}, Kenneth Rice¹²⁵, Paul M Ridker^{11

126}, Harriëtte Riese¹¹⁵, Samuli Ripatti¹¹⁷, Antonietta Robino¹²⁷, Jerome I Rotter¹²⁸, Igor Rudan³⁹, Yasaman Saba¹²⁹, Aude Saint Pierre⁴⁸, Cinzia F Sala⁴¹, Antti-Pekka Sarin¹¹⁷, Reinhold Schmidt³⁷, Rodney Scott^{76

130

131}, Marc A Seelen⁶⁷, Denis C Shields¹³², David Siscovick¹³³, Rossella Sorice^{51

134}, Alice Stanton¹³⁵, David J Stott¹³⁶, Johan Sundström¹¹⁰, Morris Swertz¹³⁷, Kent D Taylor^{138

139}, Simon Thom¹⁴⁰, Ioanna Tzoulaki⁵⁹, Christophe Tzourio^{74

75

141}, André G Uitterlinden^{12

142}; Understanding Society Scientific Group; Uwe Völker^{143

27}, Peter Vollenweider¹⁴⁴, Sarah Wild³⁹, Gonneke Willemsen¹³, Alan F Wright⁵⁸, Jie Yao²², Sébastien Thériault¹¹⁸, David Conen¹⁴⁵, John Attia^{76

130

131}, Peter Sever¹⁴⁶, Stéphanie Debette^{74

75

147}, Dennis O Mook-Kanamori^{73

148}, Eleftheria Zeggini⁷⁰, Tim D Spector⁶⁸, Pim van der Harst¹⁴⁹, Colin N A Palmer⁶⁵, Anne-Claire Vergnaud⁵⁹, Ruth J F Loos^{36

63

150}, Ozren Polasek¹⁰⁸, John M Starr^{52

151}, Giorgia Girotto^{46

47}, Caroline Hayward^{72

152}, Jaspal S Kooner^{60

82

153}, Cecila M Lindgren^{18

35}, Veronique Vitart⁵⁸, Nilesh J Samani^{7

57}, Jaakko Tuomilehto^{154

155

156

157

158}, Ulf Gyllensten⁵⁵, Paul Knekt⁴⁰, Ian J Deary^{52

86}, Marina Ciullo^{51

134}, Roberto Elosua⁵⁰, Bernard D Keavney¹⁵⁹, Andrew A Hicks⁴⁸, Robert A Scott³⁶, Paolo Gasparini^{46

47}, Maris Laan⁴⁵, YongMei Liu¹⁶⁰, Hugh Watkins^{35

42}, Catharina A Hartman¹¹⁵, Veikko Salomaa⁴⁰, Daniela Toniolo⁴¹, Markus Perola^{161

40

117}, James F Wilson^{39

58}, Helena Schmidt^{162

129}, Jing Hua Zhao³⁶, Terho Lehtimäki^{33

34}, Cornelia M van Duijn³², Vilmundur Gudnason^{30

31}, Bruce M Psaty^{29

163

164

165}, Annette Peters²⁸, Rainer Rettig¹⁶⁶, Alan James^{167

168}, J Wouter Jukema²⁵, David P Strachan¹⁶⁹, Walter Palmas¹⁷⁰, Andres Metspalu¹⁶, Erik Ingelsson^{171

172}, Dorret I Boomsma¹³, Oscar H Franco¹², Murielle Bochud²³, Christopher Newton-Cheh^{18

104

173

106}, Patricia B Munroe^{9

10}, Paul Elliott⁹⁷, Daniel I Chasman^{11

126}, Aravinda Chakravarti¹⁹, Joanne Knight¹⁷⁴, Andrew P Morris^{35

175}, Daniel Levy^{20

21}, Martin D Tobin¹, Harold Snieder², Mark J Caulfield^{9

10}, Georg B Ehret^{19

109}

Affiliations

¹ From the Department of Health Sciences (L.V.W., A.M.E., N. Shrine, C.B., T.B., M.D.T.), University of Leicester, United Kingdom.
² Department of Epidemiology (A.V., P.J.v.d.M., I.M.N., H. Snieder), University of Groningen, University Medical Center Groningen, The Netherlands.
³ Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Iran (A.V.).
⁴ Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, The Netherlands (R. Jansen).
⁵ Hebrew SeniorLife, Harvard Medical School, Boston, MA (R. Joehanes).
⁶ National Heart, Lung and Blood Institute's Framingham Heart Study, MA (R. Joehanes, A.D.J., M. Larson).
⁷ Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre (C.P.N., P.S.B., N.J.S.), University of Leicester, United Kingdom.
⁸ Institute of Psychiatry, Psychology and Neuroscience (P.F.O.), King's College London, United Kingdom.
⁹ Clinical Pharmacology, William Harvey Research Institute (C.P.C., H.R.W., M.R.B., M. Brown, B.M., M.R., P.B.M., M.J.C.).
¹⁰ NIHR Barts Cardiovascular Biomedical Research Unit (C.P.C., H.R.W., M.R.B., M. Brown, P.B.M., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom.
¹¹ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA (L.M.R., F.G., P.M.R., D.I.C.).
¹² Department of Epidemiology (G.C.V., A. Hofman, A.G.U., O.H.F.), Erasmus MC, Rotterdam, The Netherlands.
¹³ Department of Biological Psychology, Vrije Universiteit, Amsterdam, EMGO+ Institute, VU University Medical Center, The Netherlands (J.-J.H., E.J.d.G., G.W., D.I.B.).
¹⁴ Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S., M. Frånberg, A. Hamsten).
¹⁵ Centre for Molecular Medicine, Karolinska Universitetsjukhuset, Solna, Sweden (R.J.S., M. Frånberg, A. Hamsten).
¹⁶ Estonian Genome Center (T.E., E.O., A. Metspalu), University of Tartu, Estonia.
¹⁷ Divisions of Endocrinology/Children's Hospital, Boston, MA (T.E.).
¹⁸ Broad Institute of Harvard and MIT, Cambridge, MA (T.E., C.M.L., C.N.-C.).
¹⁹ Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (D.E.A., P.N., A. Chakravarti, G.B.E.).
²⁰ The Population Science Branch, Division of Intramural Research, National Heart Lung and Blood Institute (S.-J.H., D.L.), National Institutes of Health, Bethesda, MD.
²¹ The Framingham Heart Study, Framingham, MA (S.-J.H., D.L.).
²² The Institute for Translational Genomics and Population Sciences, Department of Pediatrics (X.G., J.Y.), LABioMed at Harbor-UCLA Medical Center, Torrance, CA.
²³ Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland (Z.K., M. Bochud).
²⁴ Swiss Institute of Bioinformatics, Lausanne, Switzerland (Z.K.).
²⁵ Department of Cardiology (S. Trompet, J.W.J.), Leiden University Medical Center, The Netherlands.
²⁶ Institute for Community Medicine (A.T.), University Medicine Greifswald, Germany.
²⁷ DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Germany (A.T., M.D., U.V.).
²⁸ Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany (J.S.R., A. Peters).
²⁹ Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P.), University of Washington, Seattle.
³⁰ Icelandic Heart Association, Kopavogur, Iceland (A.V.S., V. Gudnason).
³¹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland (A.V.S., V. Gudnason).
³² Genetic Epidemiology Unit, Department of Epidemiology (N.A., B.A.O., C.M.v.D.), Erasmus MC, Rotterdam, The Netherlands.
³³ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland (L.-P.L., T.L.).
³⁴ Department of Clinical Chemistry, Faculty of Medicine and Life Sciences, University of Tampere, Finland (L.-P.L., T.L.).
³⁵ Wellcome Trust Centre for Human Genetics (A. Mahajan, A.G., M. Farrall, T.F., C.M.L., H.W., A.P.M.), University of Oxford, United Kingdom.
³⁶ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, United Kingdom (N.J.W., J.L., C.L., R.J.F.L., R.A.S., J.H.Z.).
³⁷ Clinical Division of Neurogeriatrics, Department of Neurology (E.H., R. Schmidt), Medical University Graz, Austria.
³⁸ Institute of Medical Informatics, Statistics and Documentation (E.H.), Medical University Graz, Austria.
³⁹ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics (P.K.J., H.C., I.R., S.W., J.F.W.), University of Edinburgh, Scotland, United Kingdom.
⁴⁰ Department of Health (K.K., A.S.H., T. Niiranen, P.J., A.J., S. Koskinen, P.K., V.S., M.P.), Helsinki, Finland.
⁴¹ Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy (M.T., C.M.B., C.F.S., D.T.).
⁴² Division of Cardiovascular Medicine, Radcliffe Department of Medicine (A.G., M. Farrall, H.W.), University of Oxford, United Kingdom.
⁴³ Laboratory of Neurogenetics, National Institute on Aging (M.A.N.), National Institutes of Health, Bethesda, MD.
⁴⁴ Data Tecnica International, Glen Echo, MD (M.A.N.).
⁴⁵ Institute of Biomedicine and Translational Medicine (S.S., M. Laan), University of Tartu, Estonia.
⁴⁶ Medical Genetics, IRCCS-Burlo Garofolo Children Hospital, Trieste, Italy (D.V., G.G., P.G.).
⁴⁷ Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (D.V., I.G., M. Brumat, M. Cocca, A. Morgan, G.G., P.G.).
⁴⁸ Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy (F.D.G.M., P.P.P., A.S.P., A.A.H.).
⁴⁹ Department of Genetics and Genomic Sciences (K.L.A.), Icahn School of Medicine at Mount Sinai, New York.
⁵⁰ Cardiovascular Epidemiology and Genetics, IMIM, and CIBERCV, Barcelona, Spain (J. Marrugat, R.E.).
⁵¹ Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Napoli, Italy (D.R., T. Nutile, R. Sorice, M. Ciullo).
⁵² Centre for Cognitive Ageing and Cognitive Epidemiology (L.M.L., S.E.H., G.D., A.J.G., D.C.M.L., J.M.S., I.J.D.), University of Edinburgh, Scotland, United Kingdom.
⁵³ Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin (L.M.L.).
⁵⁴ UCD Conway Institute, Centre for Proteome Research (L.M.L.), University College Dublin, Belfield, Ireland.
⁵⁵ Department of Immunology, Genetics and Pathology, Uppsala Universitet, Science for Life Laboratory, Sweden (S.E., Å. Johansson, U.G.).
⁵⁶ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor (A.U.J., M. Boehnke).
⁵⁷ NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester United Kingdom (C.P.N., P.S.B., N.J.S.).
⁵⁸ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine (J.E.H., V.V., J. Marten, A.F.W., J.F.W.), University of Edinburgh, Western General Hospital, Scotland, United Kingdom.
⁵⁹ Department of Epidemiology and Biostatistics, School of Public Health (W.Z., E.E., J.C.C., H.G., B.L., I.T., A.-C.V.), Imperial College London, United Kingdom.
⁶⁰ Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, Southall, United Kingdom (W.Z., J.C.C., J.S.K.).
⁶¹ Medical Genetics Section, Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine (S.E.H.), University of Edinburgh, Western General Hospital, Scotland, United Kingdom.
⁶² Department of Medical Biology, Faculty of Medicine, University of Split, Croatia (T.Z.).
⁶³ The Charles Bronfman Institute for Personalized Medicine (Y.L., E.P.B., R.J.F.L.), Icahn School of Medicine at Mount Sinai, New York.
⁶⁴ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Greece (E.E.).
⁶⁵ Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom (N. Shah, A.S.F.D., C.N.A.P.).
⁶⁶ Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan (N. Shah).
⁶⁷ Division of Nephrology, Department of Internal Medicine (M.H.d.B., M.A.S.), University of Groningen, University Medical Center Groningen, The Netherlands.
⁶⁸ Department of Twin Research and Genetic Epidemiology (M.M., C. Menni, T.D.S.), King's College London, United Kingdom.
⁶⁹ National Institute for Health Research Biomedical Research Centre, London, United Kingdom (M.M.).
⁷⁰ Department of Human Genetics, Wellcome Trust Sanger Institute, United Kingdom (B.P.P., E.Z.).
⁷¹ Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine (A. Campbell), University of Edinburgh, Scotland, United Kingdom.
⁷² Generation Scotland, Centre for Genomic and Experimental Medicine (A. Campbell, S.P., C.H.), University of Edinburgh, Scotland, United Kingdom.
⁷³ Department of Clinical Epidemiology (R.L.-G., R.d.M., D.O.M.-K.), Leiden University Medical Center, The Netherlands.
⁷⁴ INSERM U 1219, Bordeaux Population Health Center, France (G.C., C.T., S.D.).
⁷⁵ Bordeaux University, France (G.C., C.T., S.D.).
⁷⁶ Hunter Medical Research Institute, New Lambton, NSW, Australia (C.O., E.G.H., R. Scott, J.A.).
⁷⁷ Center for Statistical Genetics, Department of Biostatistics, Ann Arbor, MI (G.A.).
⁷⁸ Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Iran (M.A.).
⁷⁹ Busselton Population Medical Research Institute, Western Australia (J.B., J.H.).
⁸⁰ PathWest Laboratory Medicine of Western Australia, Nedlands (J.B., J.H.).
⁸¹ School of Pathology and Laboratory Medicine (J.B., J.H.), The University of Western Australia, Nedlands.
⁸² Imperial College Healthcare NHS Trust, London, United Kingdom (J.C.C., J.S.K.).
⁸³ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute (F.C.), National Institutes of Health, Bethesda, MD.
⁸⁴ University of Dundee, Ninewells Hospital & Medical School, United Kingdom (J.C.).
⁸⁵ Institute of Genetic Medicine (H.J.C.), Newcastle University, Newcastle upon Tyne, United Kingdom.
⁸⁶ Department of Psychology (G.D., D.C.M.L., A. Pattie, I.J.D.), University of Edinburgh, Scotland, United Kingdom.
⁸⁷ Department of Molecular Epidemiology (J.D.), Leiden University Medical Center, The Netherlands.
⁸⁸ Center for Information Technology (Y.D., P.J.M., Q.T.N.), National Institutes of Health, Bethesda, MD.
⁸⁹ Department of Internal Medicine B (M.D.), University Medicine Greifswald, Germany.
⁹⁰ Department of Numerical Analysis and Computer Science, Stockholm University, Sweden (M. Frånberg).
⁹¹ Department of Public Health and Caring Sciences, Geriatrics, Uppsala, Sweden (V. Giedraitis).
⁹² Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt (GmbH), Neuherberg, Germany (C.G.).
⁹³ Department of Psychology, School of Social Sciences, Heriot-Watt University, Edinburgh, United Kingdom (A.J.G.).
⁹⁴ Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging (T.B.H., L.J.L.).
⁹⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A. Hofman).
⁹⁶ School of Population and Global Health (J.H.), The University of Western Australia, Nedlands.
⁹⁷ MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health (M.-R.J., P.E.), Imperial College London, United Kingdom.
⁹⁸ Center For Life-Course Health Research (M.-R.J.), University of Oulu, Finland.
⁹⁹ Biocenter Oulu (M.-R.J.), University of Oulu, Finland.
¹⁰⁰ Unit of Primary Care, Oulu University Hospital, Finland (M.-R.J.).
¹⁰¹ National Heart, Lung and Blood Institute, Cardiovascular Epidemiology and Human Genomics Branch, Bethesda, MD (A.D.J.).
¹⁰² Department of Clinical Physiology, Tampere University Hospital, Finland (M.K.).
¹⁰³ Department of Clinical Physiology, Faculty of Medicine and Life Sciences, University of Tampere, Finland (M.K.).
¹⁰⁴ Cardiovascular Research Center (S. Kathiresan, C.N.-C.).
¹⁰⁵ Center for Human Genetics (S. Kathiresan), Massachusetts General Hospital, Boston.
¹⁰⁶ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (S. Kathiresan, C.N.-C.).
¹⁰⁷ Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
¹⁰⁸ Department of Public Health, Faculty of Medicine, University of Split, Croatia (I.K., O.P.).
¹⁰⁹ Cardiology, Department of Specialties of Medicine, Geneva University Hospital, Switzerland (L. Lin, F.M., G.B.E.).
¹¹⁰ Department of Medical Sciences, Cardiovascular Epidemiology (L. Lind, J.S.), Uppsala University, Sweden.
¹¹¹ Institute of Health and Society (C. Mamasoula), Newcastle University, Newcastle upon Tyne, United Kingdom.
¹¹² Department of Psychiatry, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands (Y.M., B.W.J.H.P.).
¹¹³ School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Scotland, United Kingdom (A.D.M.).
¹¹⁴ Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston (A.C.M.).
¹¹⁵ Interdisciplinary Center Psychopathology and Emotion Regulation (IPCE) (A.J.O., H.R., C.A.H.), University of Groningen, University Medical Center Groningen, The Netherlands.
¹¹⁶ British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (S.P.), University of Glasgow, United Kingdom.
¹¹⁷ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland (A. Palotie, S.R., A.-P.S., M.P.).
¹¹⁸ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (G.P., S. Thériault).
¹¹⁹ School of Public Health (N.P.), Imperial College London, United Kingdom.
¹²⁰ Department of Neurology, General Central Hospital, Bolzano, Italy (P.P.P.).
¹²¹ Department of Neurology, University of Lübeck, Germany (P.P.P.).
¹²² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Finland (O.T.R.).
¹²³ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland (O.T.R.).
¹²⁴ Department of Cardiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China (M.R.).
¹²⁵ Departments of Biostatistics (K.R.), University of Washington, Seattle.
¹²⁶ Harvard Medical School, Boston, MA (P.M.R., D.I.C.).
¹²⁷ Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy (A.R.).
¹²⁸ The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine (J.I.R.), LABioMed at Harbor-UCLA Medical Center, Torrance, CA.
¹²⁹ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Austria (Y.S., H. Schmidt).
¹³⁰ Faculty of Health, University of Newcastle, Callaghan, NSW, Australia (R. Scott, J.A.).
¹³¹ John Hunter Hospital, New Lambton, NSW, Australia (R. Scott, J.A.).
¹³² School of Medicine, Conway Institute (D.C.S.), University College Dublin, Belfield, Ireland.
¹³³ The New York Academy of Medicine, New York (D.S.).
¹³⁴ IRCCS Neuromed, Pozzilli, Isernia, Italy (R. Sorice, M. Ciullo).
¹³⁵ Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland (A.S.).
¹³⁶ Institute of Cardiovascular and Medical Sciences, Faculty of Medicine (D.J.S.), University of Glasgow, United Kingdom.
¹³⁷ Department of Genetics, (M.S.), University of Groningen, University Medical Center Groningen, The Netherlands.
¹³⁸ Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (K.D.T.).
¹³⁹ Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (K.D.T.).
¹⁴⁰ International Centre for Circulatory Health (S. Thom), Imperial College London, United Kingdom.
¹⁴¹ Department of Public Health (C.T.), Bordeaux University Hospital, France.
¹⁴² Department of Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, The Netherlands.
¹⁴³ Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine Greifswald, Germany.
¹⁴⁴ Department of Internal Medicine, Lausanne University Hospital, CHUV, Switzerland (P.V.).
¹⁴⁵ Population Health Research Institute, McMaster University, Hamilton Ontario, Canada (D.C.).
¹⁴⁶ National Heart and Lung Institute (P.S.), Imperial College London, United Kingdom.
¹⁴⁷ Department of Neurology (S.D.), Bordeaux University Hospital, France.
¹⁴⁸ Department of Public Health and Primary Care (D.O.M.-K.), Leiden University Medical Center, The Netherlands.
¹⁴⁹ Department of Cardiology (P.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands.
¹⁵⁰ Mindich Child health Development Institute (R.J.F.L.), Icahn School of Medicine at Mount Sinai, New York.
¹⁵¹ Alzheimer Scotland Dementia Research Centre (J.M.S.), University of Edinburgh, Scotland, United Kingdom.
¹⁵² Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), University of Edinburgh, Scotland, United Kingdom.
¹⁵³ National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, United Kingdom (J.S.K.).
¹⁵⁴ Chronic Disease Prevention Unit (J.T.), Helsinki, Finland.
¹⁵⁵ National Institute for Health and Welfare (THL), Helsinki, Finland.
¹⁵⁶ Dasman Diabetes Institute, Kuwait (J.T.).
¹⁵⁷ Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia (J.T.).
¹⁵⁸ Department of Neurosciences and Preventive Medicine, Danube-University Krems, Austria (J.T.).
¹⁵⁹ Division of Cardiovascular Sciences, The University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, United Kingdom (B.D.K.).
¹⁶⁰ Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem (Y.M.L.).
¹⁶¹ Estonian Genome Center (M.P.), University of Tartu, Estonia.
¹⁶² Department of Neurology (H. Schmidt), Medical University Graz, Austria.
¹⁶³ Epidemiology (B.M.P.), University of Washington, Seattle.
¹⁶⁴ Health Services (B.M.P.), University of Washington, Seattle.
¹⁶⁵ Kaiser Permanent Washington Health Research Institute, Seattle, WA (B.M.P.).
¹⁶⁶ Institute of Physiology, University Medicine Greifswald, Karlsburg, Germany (R.R).
¹⁶⁷ School of Medicine and Pharmacology (A. James), The University of Western Australia, Nedlands.
¹⁶⁸ Department of Pulmonary Physiology and Sleep, Sir Charles Gairdner Hospital, Nedlands, Western Australia (A. James).
¹⁶⁹ Population Health Research Institute, St George's, University of London, United Kingdom (D.P.S.).
¹⁷⁰ Department of Medicine, Columbia University Medical Center, New York (W.P.).
¹⁷¹ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory (E.I.), Uppsala University, Sweden.
¹⁷² Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA (E.I.).
¹⁷³ Center for Human Genetic Research (C.N.-C.), Massachusetts General Hospital, Boston.
¹⁷⁴ Data Science Institute and Lancaster Medical School, Lancaster University, United Kingdom (J.K.).
¹⁷⁵ Department of Biostatistics, University of Liverpool, United Kingdom (A.P.M.).

PMID: 28739976
PMCID: PMC5783787
DOI: 10.1161/HYPERTENSIONAHA.117.09438

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

Louise V Wain et al. Hypertension. 2017 Sep.

. 2017 Sep;70(3):e4-e19.

doi: 10.1161/HYPERTENSIONAHA.117.09438. Epub 2017 Jul 24.

Authors

Affiliations

¹ From the Department of Health Sciences (L.V.W., A.M.E., N. Shrine, C.B., T.B., M.D.T.), University of Leicester, United Kingdom.
² Department of Epidemiology (A.V., P.J.v.d.M., I.M.N., H. Snieder), University of Groningen, University Medical Center Groningen, The Netherlands.
³ Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Iran (A.V.).
⁴ Department of Psychiatry, VU University Medical Center, Neuroscience Campus Amsterdam, The Netherlands (R. Jansen).
⁵ Hebrew SeniorLife, Harvard Medical School, Boston, MA (R. Joehanes).
⁶ National Heart, Lung and Blood Institute's Framingham Heart Study, MA (R. Joehanes, A.D.J., M. Larson).
⁷ Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre (C.P.N., P.S.B., N.J.S.), University of Leicester, United Kingdom.
⁸ Institute of Psychiatry, Psychology and Neuroscience (P.F.O.), King's College London, United Kingdom.
⁹ Clinical Pharmacology, William Harvey Research Institute (C.P.C., H.R.W., M.R.B., M. Brown, B.M., M.R., P.B.M., M.J.C.).
¹⁰ NIHR Barts Cardiovascular Biomedical Research Unit (C.P.C., H.R.W., M.R.B., M. Brown, P.B.M., M.J.C.), Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom.
¹¹ Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA (L.M.R., F.G., P.M.R., D.I.C.).
¹² Department of Epidemiology (G.C.V., A. Hofman, A.G.U., O.H.F.), Erasmus MC, Rotterdam, The Netherlands.
¹³ Department of Biological Psychology, Vrije Universiteit, Amsterdam, EMGO+ Institute, VU University Medical Center, The Netherlands (J.-J.H., E.J.d.G., G.W., D.I.B.).
¹⁴ Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden (R.J.S., M. Frånberg, A. Hamsten).
¹⁵ Centre for Molecular Medicine, Karolinska Universitetsjukhuset, Solna, Sweden (R.J.S., M. Frånberg, A. Hamsten).
¹⁶ Estonian Genome Center (T.E., E.O., A. Metspalu), University of Tartu, Estonia.
¹⁷ Divisions of Endocrinology/Children's Hospital, Boston, MA (T.E.).
¹⁸ Broad Institute of Harvard and MIT, Cambridge, MA (T.E., C.M.L., C.N.-C.).
¹⁹ Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (D.E.A., P.N., A. Chakravarti, G.B.E.).
²⁰ The Population Science Branch, Division of Intramural Research, National Heart Lung and Blood Institute (S.-J.H., D.L.), National Institutes of Health, Bethesda, MD.
²¹ The Framingham Heart Study, Framingham, MA (S.-J.H., D.L.).
²² The Institute for Translational Genomics and Population Sciences, Department of Pediatrics (X.G., J.Y.), LABioMed at Harbor-UCLA Medical Center, Torrance, CA.
²³ Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland (Z.K., M. Bochud).
²⁴ Swiss Institute of Bioinformatics, Lausanne, Switzerland (Z.K.).
²⁵ Department of Cardiology (S. Trompet, J.W.J.), Leiden University Medical Center, The Netherlands.
²⁶ Institute for Community Medicine (A.T.), University Medicine Greifswald, Germany.
²⁷ DZHK (German Centre for Cardiovascular Research), partner site Greifswald, Germany (A.T., M.D., U.V.).
²⁸ Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany (J.S.R., A. Peters).
²⁹ Cardiovascular Health Research Unit, Department of Medicine (J.C.B., B.M.P.), University of Washington, Seattle.
³⁰ Icelandic Heart Association, Kopavogur, Iceland (A.V.S., V. Gudnason).
³¹ Faculty of Medicine, University of Iceland, Reykjavik, Iceland (A.V.S., V. Gudnason).
³² Genetic Epidemiology Unit, Department of Epidemiology (N.A., B.A.O., C.M.v.D.), Erasmus MC, Rotterdam, The Netherlands.
³³ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland (L.-P.L., T.L.).
³⁴ Department of Clinical Chemistry, Faculty of Medicine and Life Sciences, University of Tampere, Finland (L.-P.L., T.L.).
³⁵ Wellcome Trust Centre for Human Genetics (A. Mahajan, A.G., M. Farrall, T.F., C.M.L., H.W., A.P.M.), University of Oxford, United Kingdom.
³⁶ MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, United Kingdom (N.J.W., J.L., C.L., R.J.F.L., R.A.S., J.H.Z.).
³⁷ Clinical Division of Neurogeriatrics, Department of Neurology (E.H., R. Schmidt), Medical University Graz, Austria.
³⁸ Institute of Medical Informatics, Statistics and Documentation (E.H.), Medical University Graz, Austria.
³⁹ Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics (P.K.J., H.C., I.R., S.W., J.F.W.), University of Edinburgh, Scotland, United Kingdom.
⁴⁰ Department of Health (K.K., A.S.H., T. Niiranen, P.J., A.J., S. Koskinen, P.K., V.S., M.P.), Helsinki, Finland.
⁴¹ Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milano, Italy (M.T., C.M.B., C.F.S., D.T.).
⁴² Division of Cardiovascular Medicine, Radcliffe Department of Medicine (A.G., M. Farrall, H.W.), University of Oxford, United Kingdom.
⁴³ Laboratory of Neurogenetics, National Institute on Aging (M.A.N.), National Institutes of Health, Bethesda, MD.
⁴⁴ Data Tecnica International, Glen Echo, MD (M.A.N.).
⁴⁵ Institute of Biomedicine and Translational Medicine (S.S., M. Laan), University of Tartu, Estonia.
⁴⁶ Medical Genetics, IRCCS-Burlo Garofolo Children Hospital, Trieste, Italy (D.V., G.G., P.G.).
⁴⁷ Department of Medical, Surgical and Health Sciences, University of Trieste, Italy (D.V., I.G., M. Brumat, M. Cocca, A. Morgan, G.G., P.G.).
⁴⁸ Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lübeck, Bolzano, Italy (F.D.G.M., P.P.P., A.S.P., A.A.H.).
⁴⁹ Department of Genetics and Genomic Sciences (K.L.A.), Icahn School of Medicine at Mount Sinai, New York.
⁵⁰ Cardiovascular Epidemiology and Genetics, IMIM, and CIBERCV, Barcelona, Spain (J. Marrugat, R.E.).
⁵¹ Institute of Genetics and Biophysics A. Buzzati-Traverso, CNR, Napoli, Italy (D.R., T. Nutile, R. Sorice, M. Ciullo).
⁵² Centre for Cognitive Ageing and Cognitive Epidemiology (L.M.L., S.E.H., G.D., A.J.G., D.C.M.L., J.M.S., I.J.D.), University of Edinburgh, Scotland, United Kingdom.
⁵³ Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin (L.M.L.).
⁵⁴ UCD Conway Institute, Centre for Proteome Research (L.M.L.), University College Dublin, Belfield, Ireland.
⁵⁵ Department of Immunology, Genetics and Pathology, Uppsala Universitet, Science for Life Laboratory, Sweden (S.E., Å. Johansson, U.G.).
⁵⁶ Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor (A.U.J., M. Boehnke).
⁵⁷ NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester United Kingdom (C.P.N., P.S.B., N.J.S.).
⁵⁸ MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine (J.E.H., V.V., J. Marten, A.F.W., J.F.W.), University of Edinburgh, Western General Hospital, Scotland, United Kingdom.
⁵⁹ Department of Epidemiology and Biostatistics, School of Public Health (W.Z., E.E., J.C.C., H.G., B.L., I.T., A.-C.V.), Imperial College London, United Kingdom.
⁶⁰ Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, Southall, United Kingdom (W.Z., J.C.C., J.S.K.).
⁶¹ Medical Genetics Section, Centre for Genomic and Experimental Medicine and MRC Institute of Genetics and Molecular Medicine (S.E.H.), University of Edinburgh, Western General Hospital, Scotland, United Kingdom.
⁶² Department of Medical Biology, Faculty of Medicine, University of Split, Croatia (T.Z.).
⁶³ The Charles Bronfman Institute for Personalized Medicine (Y.L., E.P.B., R.J.F.L.), Icahn School of Medicine at Mount Sinai, New York.
⁶⁴ Department of Hygiene and Epidemiology, University of Ioannina Medical School, Greece (E.E.).
⁶⁵ Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Scotland, United Kingdom (N. Shah, A.S.F.D., C.N.A.P.).
⁶⁶ Department of Pharmacy, COMSATS Institute of Information Technology, Abbottabad, Pakistan (N. Shah).
⁶⁷ Division of Nephrology, Department of Internal Medicine (M.H.d.B., M.A.S.), University of Groningen, University Medical Center Groningen, The Netherlands.
⁶⁸ Department of Twin Research and Genetic Epidemiology (M.M., C. Menni, T.D.S.), King's College London, United Kingdom.
⁶⁹ National Institute for Health Research Biomedical Research Centre, London, United Kingdom (M.M.).
⁷⁰ Department of Human Genetics, Wellcome Trust Sanger Institute, United Kingdom (B.P.P., E.Z.).
⁷¹ Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine (A. Campbell), University of Edinburgh, Scotland, United Kingdom.
⁷² Generation Scotland, Centre for Genomic and Experimental Medicine (A. Campbell, S.P., C.H.), University of Edinburgh, Scotland, United Kingdom.
⁷³ Department of Clinical Epidemiology (R.L.-G., R.d.M., D.O.M.-K.), Leiden University Medical Center, The Netherlands.
⁷⁴ INSERM U 1219, Bordeaux Population Health Center, France (G.C., C.T., S.D.).
⁷⁵ Bordeaux University, France (G.C., C.T., S.D.).
⁷⁶ Hunter Medical Research Institute, New Lambton, NSW, Australia (C.O., E.G.H., R. Scott, J.A.).
⁷⁷ Center for Statistical Genetics, Department of Biostatistics, Ann Arbor, MI (G.A.).
⁷⁸ Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Iran (M.A.).
⁷⁹ Busselton Population Medical Research Institute, Western Australia (J.B., J.H.).
⁸⁰ PathWest Laboratory Medicine of Western Australia, Nedlands (J.B., J.H.).
⁸¹ School of Pathology and Laboratory Medicine (J.B., J.H.), The University of Western Australia, Nedlands.
⁸² Imperial College Healthcare NHS Trust, London, United Kingdom (J.C.C., J.S.K.).
⁸³ Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute (F.C.), National Institutes of Health, Bethesda, MD.
⁸⁴ University of Dundee, Ninewells Hospital & Medical School, United Kingdom (J.C.).
⁸⁵ Institute of Genetic Medicine (H.J.C.), Newcastle University, Newcastle upon Tyne, United Kingdom.
⁸⁶ Department of Psychology (G.D., D.C.M.L., A. Pattie, I.J.D.), University of Edinburgh, Scotland, United Kingdom.
⁸⁷ Department of Molecular Epidemiology (J.D.), Leiden University Medical Center, The Netherlands.
⁸⁸ Center for Information Technology (Y.D., P.J.M., Q.T.N.), National Institutes of Health, Bethesda, MD.
⁸⁹ Department of Internal Medicine B (M.D.), University Medicine Greifswald, Germany.
⁹⁰ Department of Numerical Analysis and Computer Science, Stockholm University, Sweden (M. Frånberg).
⁹¹ Department of Public Health and Caring Sciences, Geriatrics, Uppsala, Sweden (V. Giedraitis).
⁹² Helmholtz Zentrum Muenchen, Deutsches Forschungszentrum fuer Gesundheit und Umwelt (GmbH), Neuherberg, Germany (C.G.).
⁹³ Department of Psychology, School of Social Sciences, Heriot-Watt University, Edinburgh, United Kingdom (A.J.G.).
⁹⁴ Intramural Research Program, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging (T.B.H., L.J.L.).
⁹⁵ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A. Hofman).
⁹⁶ School of Population and Global Health (J.H.), The University of Western Australia, Nedlands.
⁹⁷ MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health (M.-R.J., P.E.), Imperial College London, United Kingdom.
⁹⁸ Center For Life-Course Health Research (M.-R.J.), University of Oulu, Finland.
⁹⁹ Biocenter Oulu (M.-R.J.), University of Oulu, Finland.
¹⁰⁰ Unit of Primary Care, Oulu University Hospital, Finland (M.-R.J.).
¹⁰¹ National Heart, Lung and Blood Institute, Cardiovascular Epidemiology and Human Genomics Branch, Bethesda, MD (A.D.J.).
¹⁰² Department of Clinical Physiology, Tampere University Hospital, Finland (M.K.).
¹⁰³ Department of Clinical Physiology, Faculty of Medicine and Life Sciences, University of Tampere, Finland (M.K.).
¹⁰⁴ Cardiovascular Research Center (S. Kathiresan, C.N.-C.).
¹⁰⁵ Center for Human Genetics (S. Kathiresan), Massachusetts General Hospital, Boston.
¹⁰⁶ Program in Medical and Population Genetics, Broad Institute, Cambridge, MA (S. Kathiresan, C.N.-C.).
¹⁰⁷ Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, United Kingdom (K.-T.K.).
¹⁰⁸ Department of Public Health, Faculty of Medicine, University of Split, Croatia (I.K., O.P.).
¹⁰⁹ Cardiology, Department of Specialties of Medicine, Geneva University Hospital, Switzerland (L. Lin, F.M., G.B.E.).
¹¹⁰ Department of Medical Sciences, Cardiovascular Epidemiology (L. Lind, J.S.), Uppsala University, Sweden.
¹¹¹ Institute of Health and Society (C. Mamasoula), Newcastle University, Newcastle upon Tyne, United Kingdom.
¹¹² Department of Psychiatry, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands (Y.M., B.W.J.H.P.).
¹¹³ School of Molecular, Genetic and Population Health Sciences, University of Edinburgh, Medical School, Teviot Place, Scotland, United Kingdom (A.D.M.).
¹¹⁴ Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston (A.C.M.).
¹¹⁵ Interdisciplinary Center Psychopathology and Emotion Regulation (IPCE) (A.J.O., H.R., C.A.H.), University of Groningen, University Medical Center Groningen, The Netherlands.
¹¹⁶ British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences (S.P.), University of Glasgow, United Kingdom.
¹¹⁷ Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland (A. Palotie, S.R., A.-P.S., M.P.).
¹¹⁸ Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada (G.P., S. Thériault).
¹¹⁹ School of Public Health (N.P.), Imperial College London, United Kingdom.
¹²⁰ Department of Neurology, General Central Hospital, Bolzano, Italy (P.P.P.).
¹²¹ Department of Neurology, University of Lübeck, Germany (P.P.P.).
¹²² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Finland (O.T.R.).
¹²³ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland (O.T.R.).
¹²⁴ Department of Cardiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China (M.R.).
¹²⁵ Departments of Biostatistics (K.R.), University of Washington, Seattle.
¹²⁶ Harvard Medical School, Boston, MA (P.M.R., D.I.C.).
¹²⁷ Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy (A.R.).
¹²⁸ The Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine (J.I.R.), LABioMed at Harbor-UCLA Medical Center, Torrance, CA.
¹²⁹ Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Austria (Y.S., H. Schmidt).
¹³⁰ Faculty of Health, University of Newcastle, Callaghan, NSW, Australia (R. Scott, J.A.).
¹³¹ John Hunter Hospital, New Lambton, NSW, Australia (R. Scott, J.A.).
¹³² School of Medicine, Conway Institute (D.C.S.), University College Dublin, Belfield, Ireland.
¹³³ The New York Academy of Medicine, New York (D.S.).
¹³⁴ IRCCS Neuromed, Pozzilli, Isernia, Italy (R. Sorice, M. Ciullo).
¹³⁵ Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin 2, Ireland (A.S.).
¹³⁶ Institute of Cardiovascular and Medical Sciences, Faculty of Medicine (D.J.S.), University of Glasgow, United Kingdom.
¹³⁷ Department of Genetics, (M.S.), University of Groningen, University Medical Center Groningen, The Netherlands.
¹³⁸ Institute for Translational Genomics and Population Sciences, Los Angeles BioMedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA (K.D.T.).
¹³⁹ Division of Genetic Outcomes, Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA (K.D.T.).
¹⁴⁰ International Centre for Circulatory Health (S. Thom), Imperial College London, United Kingdom.
¹⁴¹ Department of Public Health (C.T.), Bordeaux University Hospital, France.
¹⁴² Department of Internal Medicine (A.G.U.), Erasmus MC, Rotterdam, The Netherlands.
¹⁴³ Interfaculty Institute for Genetics and Functional Genomics (U.V.), University Medicine Greifswald, Germany.
¹⁴⁴ Department of Internal Medicine, Lausanne University Hospital, CHUV, Switzerland (P.V.).
¹⁴⁵ Population Health Research Institute, McMaster University, Hamilton Ontario, Canada (D.C.).
¹⁴⁶ National Heart and Lung Institute (P.S.), Imperial College London, United Kingdom.
¹⁴⁷ Department of Neurology (S.D.), Bordeaux University Hospital, France.
¹⁴⁸ Department of Public Health and Primary Care (D.O.M.-K.), Leiden University Medical Center, The Netherlands.
¹⁴⁹ Department of Cardiology (P.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands.
¹⁵⁰ Mindich Child health Development Institute (R.J.F.L.), Icahn School of Medicine at Mount Sinai, New York.
¹⁵¹ Alzheimer Scotland Dementia Research Centre (J.M.S.), University of Edinburgh, Scotland, United Kingdom.
¹⁵² Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine (C.H.), University of Edinburgh, Scotland, United Kingdom.
¹⁵³ National Heart and Lung Institute, Imperial College London, Hammersmith Hospital Campus, United Kingdom (J.S.K.).
¹⁵⁴ Chronic Disease Prevention Unit (J.T.), Helsinki, Finland.
¹⁵⁵ National Institute for Health and Welfare (THL), Helsinki, Finland.
¹⁵⁶ Dasman Diabetes Institute, Kuwait (J.T.).
¹⁵⁷ Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia (J.T.).
¹⁵⁸ Department of Neurosciences and Preventive Medicine, Danube-University Krems, Austria (J.T.).
¹⁵⁹ Division of Cardiovascular Sciences, The University of Manchester and Central Manchester University Hospitals NHS Foundation Trust, United Kingdom (B.D.K.).
¹⁶⁰ Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem (Y.M.L.).
¹⁶¹ Estonian Genome Center (M.P.), University of Tartu, Estonia.
¹⁶² Department of Neurology (H. Schmidt), Medical University Graz, Austria.
¹⁶³ Epidemiology (B.M.P.), University of Washington, Seattle.
¹⁶⁴ Health Services (B.M.P.), University of Washington, Seattle.
¹⁶⁵ Kaiser Permanent Washington Health Research Institute, Seattle, WA (B.M.P.).
¹⁶⁶ Institute of Physiology, University Medicine Greifswald, Karlsburg, Germany (R.R).
¹⁶⁷ School of Medicine and Pharmacology (A. James), The University of Western Australia, Nedlands.
¹⁶⁸ Department of Pulmonary Physiology and Sleep, Sir Charles Gairdner Hospital, Nedlands, Western Australia (A. James).
¹⁶⁹ Population Health Research Institute, St George's, University of London, United Kingdom (D.P.S.).
¹⁷⁰ Department of Medicine, Columbia University Medical Center, New York (W.P.).
¹⁷¹ Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory (E.I.), Uppsala University, Sweden.
¹⁷² Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA (E.I.).
¹⁷³ Center for Human Genetic Research (C.N.-C.), Massachusetts General Hospital, Boston.
¹⁷⁴ Data Science Institute and Lancaster Medical School, Lancaster University, United Kingdom (J.K.).
¹⁷⁵ Department of Biostatistics, University of Liverpool, United Kingdom (A.P.M.).

PMID: 28739976
PMCID: PMC5783787
DOI: 10.1161/HYPERTENSIONAHA.117.09438

Abstract

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

Keywords: GWAS; blood pressure; cardiovascular risk; complex traits; eSNP; hypertension.

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Conflict of interest statement

Disclosures

We declare competing financial interests (see corresponding section in the online-only Data Supplement).

Figures

**Figure**
Overlap of expression quantitative trait loci (eQTL) evidence from 4 whole-blood and 1 kidney resource. The figure indicates overlap of evidence for eQTLs from 4 whole-blood studies (SABRe, NESDA-NTR, BIOS, and GTEx) and from 1 kidney resource (TransplantLines). Every colored line indicates that this gene was analysis-wide significant in a given resource. Only genes identified by at least 2 resources are shown. The genes are sorted by genomic position on the y axis.

See this image and copyright information in PMC

References

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Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

Affiliations

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous