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

Ayush Giri ORCID logo; Jacklyn N Hellwege ORCID logo; Jacob M Keaton; Jihwan Park; Chengxiang Qiu; Helen R Warren; Eric S Torstenson; Csaba P Kovesdy; Yan V Sun; Otis D Wilson; +92 more... Cassianne Robinson-Cohen; Christianne L Roumie; Cecilia P Chung; Kelly A Birdwell; Scott M Damrauer; Scott L DuVall ORCID logo; Derek Klarin; Kelly Cho; Yu Wang; Evangelos Evangelou ORCID logo; Claudia P Cabrera; Louise V Wain ORCID logo; Rojesh Shrestha; Brian S Mautz; Elvis A Akwo; Muralidharan Sargurupremraj; Stéphanie Debette; Michael Boehnke ORCID logo; Laura J Scott; Jian'an Luan; Jing-Hua Zhao; Sara M Willems; Sébastien Thériault; Nabi Shah ORCID logo; Christopher Oldmeadow; Peter Almgren ORCID logo; Ruifang Li-Gao; Niek Verweij ORCID logo; Thibaud S Boutin ORCID logo; Massimo Mangino ORCID logo; Ioanna Ntalla; Elena Feofanova ORCID logo; Praveen Surendran; James P Cook; Savita Karthikeyan; Najim Lahrouchi; Chunyu Liu; Nuno Sepúlveda; Tom G Richardson; Aldi Kraja; Philippe Amouyel ORCID logo; Martin Farrall; Neil R Poulter; Understanding Society Scientific Group; International Consortium for Blood Pressure; Blood Pressure-International Consortium of Exome Chip Studies; Markku Laakso; Eleftheria Zeggini ORCID logo; Peter Sever; Robert A Scott; Claudia Langenberg; Nicholas J Wareham; David Conen; Colin Neil Alexander Palmer ORCID logo; John Attia ORCID logo; Daniel I Chasman; Paul M Ridker; Olle Melander; Dennis Owen Mook-Kanamori; Pim van der Harst ORCID logo; Francesco Cucca ORCID logo; David Schlessinger; Caroline Hayward ORCID logo; Tim D Spector; Marjo-Riitta Jarvelin; Branwen J Hennig; Nicholas J Timpson; Wei-Qi Wei; Joshua C Smith; Yaomin Xu; Michael E Matheny; Edward E Siew; Cecilia Lindgren; Karl-Heinz Herzig; George Dedoussis; Joshua C Denny; Bruce M Psaty; Joanna MM Howson ORCID logo; Patricia B Munroe ORCID logo; Christopher Newton-Cheh; Mark J Caulfield ORCID logo; Paul Elliott ORCID logo; J Michael Gaziano; John Concato; Peter WF Wilson; Philip S Tsao; Digna R Velez Edwards; Katalin Susztak ORCID logo; Million Veteran Program; Christopher J O'Donnell; Adriana M Hung ORCID logo; Todd L Edwards ORCID logo; (2018) Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nature genetics, 51 (1). pp. 51-62. ISSN 1061-4036 DOI: 10.1038/s41588-018-0303-9
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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.


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