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Trans-ethnic association study of blood pressure determinants in over 750,000 individuals

2018; Nature Portfolio; Volume: 51; Issue: 1 Linguagem: Inglês

10.1038/s41588-018-0303-9

1546-1718

Ayush Giri, Jacklyn N. Hellwege, Jacob M. Keaton, Jihwan Park, Chengxiang Qiu, Helen Warren, Eric S. Torstenson, Csaba P. Kövesdy, Yan V. Sun, Otis D. Wilson, Cassianne Robinson‐Cohen, Christianne L. Roumie, Cecilia P. Chung, Kelly A. Birdwell, Scott M. Damrauer, Scott L. DuVall, Derek Klarin, Kelly Cho, Yu Wang, Εvangelos Εvangelou, Claudia P. Cabrera, Louise V. Wain, Rojesh Shrestha, Brian S. Mautz, Elvis A. Akwo, Muralidharan Sargurupremraj, Stéphanie Debette, Michael Boehnke, Laura J. Scott, Jian’an Luan, Jing-Hua Zhao, Sara M. Willems, Sébastien Thériault, Nabi Shah, Christopher Oldmeadow, Peter Almgren, Ruifang Li‐Gao, Niek Verweij, Thibaud Boutin, Massimo Mangino, Ioanna Ntalla, Elena V. Feofanova, Praveen Surendran, James P. Cook, Savita Karthikeyan, Najim Lahrouchi, Chunyu Liu, Nuno Sepúlveda, Tom G. Richardson, Aldi T. Kraja, Philippe Amouyel, Martin Farrall, Neil R Poulter, Markku Laakso, Eleftheria Zeggini, Peter Sever, Robert A. Scott, Claudia Langenberg, Nicholas J. Wareham, David Conen, Nicholette D. Palmer, John Attia, Daniel I. Chasman, Paul M. Ridker, Olle Melander, Dennis Owen Mook-Kanamori, Pim van der Harst, Francesco Cucca, David Schlessinger, Caroline Hayward, Tim D. Spector, Marjo-Riitta Jarvelin, Branwen J. Hennig, Nicholas J. Timpson, Wei-Qi Wei, Joshua C. Smith, Yaomin Xu, Michael E. Matheny, Edward D. Siew, Cecilia M. Lindgren, Karl‐Heinz Herzig, George Dedoussis, Joshua C. Denny, Bruce M. Psaty, Joanna M. M. Howson, Patricia B. Munroe, Christopher Newton‐Cheh, Mark J. Caulfield, Paul Elliott, J. Michael Gaziano, John Concato, Peter W.F. Wilson, Philip S. Tsao, Digna R. Velez Edwards, Katalin Suszták, Christopher J. O’Donnell, Adriana M. Hung, Todd L. Edwards,

Hormonal Regulation and Hypertension

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. Analysis of blood pressure data from the Million Veteran Program trans-ethnic cohort identifies common and rare variants, and genetically predicted gene expression across multiple tissues associated with systolic, diastolic and pulse pressure in over 775,000 individuals.