The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals · SciRah

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The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Georg Ehret^{a b}, Teresa Cruz Ferreira^c, Daniel I. Chasman^{d e}, Anne Jackson^{f g}, Ellen M. Schmidt^h, Toby Johnson^{i j}, Guðmar Þorleifsson^k, Jian’an Luan^l, Louise A Donnelly^m, Stavroula Kanoniⁿ, Ann-Kristin Petersen^o, Vasyl Pihur

Nature Genetics Nature Portfolio2016-09-12 420 citations49 references

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Abstract

To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure-associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure-related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.

TL;DRThe 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney, expanding current knowledge of blood pressure–related pathways and highlighting tissues beyond the classical renal system in blood pressure regulation. (Semantic Scholar)

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^aCardiology, Department of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland
^bCenter for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
^cWellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK
^dDivision of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave. East, Boston, MA 02215, USA
^eHarvard Medical School, Boston, MA 02115, USA
^fCenter for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA
^gDepartment of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA
^hDepartment of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
ⁱClinical Pharmacology, William Harvey Research Institute, Queen Mary University of London, London, EC1M 6BQ, UK
^jGlaxoSmithKline, Gunnels Wood Road, Stevenage SG1 2NY, UK
^kdeCODE Genetics/Amgen, Inc., Reykjavik, Iceland
^lMRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK
^mMedical Research Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK
ⁿWilliam Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
^oInstitute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany
^pCardiovascular Research Unit, Center for Molecular Medicine L8:03, Department of Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden
^qCenter for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden
^rDepartment of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, SE-205 02 Malmö, Sweden
^sDepartment of Odontology, Umeå University, Sweden
^tDepartment of Public Health and Clinical Medicine, Umeå University, Sweden
^uCentre of Excellence for Public Health, Queens University Belfast, Grosvenor Road, Belfast BT126JP, UK
^vLaboratory of Genetics, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
^wDepartment of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK
^xINSERM UMR970, Paris Cardiovascular Research Center PARCC, 56 rue Leblanc, 75015 Paris, France
^yUniversity Paris-Descartes, Sorbonne Paris Cité, 12 rue de l'Ecole de medicine, F-75006 Paris, France
^zInstitute for Molecular Medicine Finland FIMM, University of Helsinki, 00290 Helsinki, Finland
^aaNational Institute for Health and Welfare, FI-00271 Helsinki, Finland
^abGenetic Epidemiology Group, Dept. Epidemiology and Public Health, UCL, London, WC1E 6BT, UK
^acVth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany
^adInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 W. Carson Street, Torrance, CA 90502, USA
^aeDepartment of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland
^afDepartment of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland
^agUniversity of Lund, Dept Internal Medicine, Malmo, SE 20502, Sweden
^ahUniversity of Verona, Dept of Internal Medicine, Verona, Italy 37134
^aiUppsala University, Uppsala Clinical Research Center, SE-75185 Uppsala, Sweden
^ajDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
^akDept of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, SE-171 77 Stockholm, Sweden
^alDepartment of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
^amSecond Department of Cardiology, Attikon Hospital, School of Medicine, University of Athens, Athens, Greece
^anChildren's Hospital Oakland Research Institute, Oakland, CA 94609, USA