Open AccessTrans-ethnic association study of blood pressure determinants in over 750,000 individuals
Author(s) -
Ayush Giri,
Jacklyn N. Hellwege,
Jacob M. Keaton,
Jihwan Park,
Chengxiang Qiu,
Helen R. Warren,
Eric S. Torstenson,
Csaba P. Kövesdy,
Yan V. Sun,
Otis Wilson,
Cassianne RobinsonCohen,
Christianne L. Roumie,
Cecilia P. Chung,
Kelly A. Birdwell,
Scott M. Damrauer,
Scott L. DuVall,
Derek Klarin,
K Cho,
Yu Wang,
Εvangelos Εvangelou,
Claudia 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 Zhao,
Sara M. Willems,
Sébastien Thériault,
Nabi Shah,
Christopher Oldmeadow,
Peter Almgren,
Ruifang LiGao,
Niek Verweij,
Thibaud Boutin,
Massimo Mangino,
Ιωάννα Ντάλλα,
Elena V. Feofanova,
Praveen Surendran,
James Cook,
Savita Karthikeyan,
Najim Lahrouchi,
C Liu,
Nuno Sepúlveda,
Tom G Richardson,
Aldi T. Kraja,
Philippe Amouyel,
Martin Farrall,
Neil Poulter,
Markku Laakso,
Eleftheria Zeggini,
Peter Sever,
Robert A. Scott,
Claudia Langenberg,
Nicholas J. Wareham,
David Conen,
Colin N.A. Palmer,
John Attia,
Daniel I. Chasman,
Paul M. Ridker,
Olle Melander,
Dennis O. MookKanamori,
Harst Pvd.,
Francesco Cucca,
David Schlessinger,
Caroline Hayward,
Timothy D. Spector,
MarjoRiitta Järvelin,
Branwen J. Hennig,
Nicholas J. Timpson,
Wei W-Q.,
Joshua C. Smith,
Yu Xu,
Michael E. Matheny,
Edward Siew,
Cecilia M. Lindgren,
Herzig Kh,
George Dedoussis,
Joshua C. Denny,
Bruce M. Psaty,
Howson Jmm.,
Patricia B. Munroe,
Christopher NewtonCheh,
Mark J. Caulfield,
Paul Elliott,
J. Michael Gaziano,
John Concato,
Wilson Pwf,
Philip S. Tsao,
Velez Edwards,
Katalin Suszták,
Christopher J. O’Donnell,
Adriana M. Hung,
Todd L. Edwards
Publication year - 2018
Publication title -
nature genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 18.861
H-Index - 573
eISSN - 1546-1718
pISSN - 1061-4036
DOI - 10.1038/s41588-018-0303-9
Subject(s) - blood pressure , biology , phenome , transcriptome , gene , single nucleotide polymorphism , genome wide association study , genetic association , pulse pressure , genetics , genetic architecture , gene expression , genome , endocrinology , genotype , quantitative trait locus
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.