1. Trans-ethnic association study of blood pressure determinants in over 750,000 individuals
- Author
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Dennis O. Mook-Kanamori, J M Gaziano, Harst Pvd., Derek Klarin, K A Birdwell, Josh C. Denny, Martin Farrall, Thibaud Boutin, Najim Lahrouchi, Nabi Shah, Scott M. Damrauer, Cecilia P. Chung, Neil Poulter, Herzig K-H., E E Siew, John Concato, Yan V. Sun, Sara M. Willems, Louise V. Wain, Philip S. Tsao, Massimo Mangino, Wei W-Q., Ioanna Ntalla, Brian S. Mautz, David Schlessinger, Daniel I. Chasman, Branwen J. Hennig, Christopher Newton-Cheh, Michael E. Matheny, Palmer Cna., Caroline Hayward, Zhao J-H., Eleftheria Zeggini, Paul Elliott, C M Lindgren, Praveen Surendran, Csaba P. Kovesdy, Jacob M. Keaton, Chengxiang Qiu, Claudia Langenberg, Christopher Oldmeadow, Stéphanie Debette, D.R. Velez Edwards, Evangelos Evangelou, Howson Jmm., Adriana M. Hung, Yaomin Xu, Nicholas J. Wareham, James P. Cook, Scott L. DuVall, Peter Almgren, Jacklyn N. Hellwege, Sébastien Thériault, Helen R. Warren, Jian'an Luan, Ching-Ti Liu, Christopher J. O'Donnell, Michael Boehnke, Peter S. Sever, Ruifang Li-Gao, Cassianne Robinson-Cohen, Robert A. Scott, Muralidharan Sargurupremraj, Mark J. Caulfield, Jarvelin M-R., Tim D. Spector, Todd L. Edwards, Elena V. Feofanova, Francesco Cucca, Jihwan Park, Savita Karthikeyan, J C Smith, Wilson Pwf., Markku Laakso, Ayush Giri, Christianne L. Roumie, Rojesh Shrestha, Claudia P. Cabrera, Kelly Cho, Laura J. Scott, Elvis A. Akwo, Yu Wang, Tom G. Richardson, Patricia B. Munroe, Eric S. Torstenson, Katalin Susztak, John Attia, Bruce M. Psaty, Aldi T. Kraja, Olle Melander, Nicholas J. Timpson, George Dedoussis, Paul M. Ridker, Niek Verweij, David Conen, Philippe Amouyel, Otis D. Wilson, Nuno Sepúlveda, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiology, ACS - Heart failure & arrhythmias, Cardiovascular Centre (CVC), Luan, Jian'an [0000-0003-3137-6337], Zhao, Jing Hua [0000-0003-4930-3582], Surendran, Praveen [0000-0002-4911-6077], Karthikeyan, Savita [0000-0002-4798-5746], Langenberg, Claudia [0000-0002-5017-7344], Wareham, Nicholas [0000-0003-1422-2993], Howson, Joanna [0000-0001-7618-0050], and Apollo - University of Cambridge Repository
- Subjects
Male ,LOCI ,Gene Expression ,Physiology ,Blood Pressure ,Genome-wide association study ,IDENTIFIES 8 ,Mice ,0302 clinical medicine ,Ethnicity ,PARTITIONING HERITABILITY ,Genetics & Heredity ,0303 health sciences ,Kidney ,Blood Pressure-International Consortium of Exome Chip Studies ,Million Veteran Program ,PULSE PRESSURE ,11 Medical And Health Sciences ,Middle Aged ,Up-Regulation ,3. Good health ,Pulse pressure ,Kidney Tubules ,medicine.anatomical_structure ,VINTAGE ,International Consortium for Blood Pressure ,AUTOSOMAL-DOMINANT HYPERTENSION ,Female ,Life Sciences & Biomedicine ,Understanding Society Scientific Group ,Adolescent ,Diastole ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Genetics ,medicine ,Animals ,Humans ,GENOME-WIDE ASSOCIATION ,Gene ,030304 developmental biology ,Genetic association ,Science & Technology ,06 Biological Sciences ,GLOBAL BURDEN ,MEAN ARTERIAL ,GENE ,Blood pressure ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,SOLUBLE GUANYLYL CYCLASE ,Transcriptome ,030217 neurology & neurosurgery ,Genome-Wide Association Study ,Developmental Biology - Abstract
International audience; In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.
- Published
- 2019
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