TY - JOUR
T1 - Trans-ethnic association study of blood pressure determinants in over 750,000 individuals
AU - Understanding Society Scientific Group
AU - International Consortium for Blood Pressure
AU - Blood Pressure-International Consortium of Exome Chip Studies
AU - Million Veteran Program
AU - Giri, Ayush
AU - Hellwege, Jacklyn N.
AU - Keaton, Jacob M.
AU - Park, Jihwan
AU - Qiu, Chengxiang
AU - Warren, Helen R.
AU - Torstenson, Eric S.
AU - Kovesdy, Csaba P.
AU - Sun, Yan V.
AU - Wilson, Otis D.
AU - Robinson-Cohen, Cassianne
AU - Roumie, Christianne L.
AU - Chung, Cecilia P.
AU - Birdwell, Kelly A.
AU - Damrauer, Scott M.
AU - DuVall, Scott L.
AU - Klarin, Derek
AU - Cho, Kelly
AU - Wang, Yu
AU - Evangelou, Evangelos
AU - Cabrera, Claudia P.
AU - Wain, Louise V.
AU - Shrestha, Rojesh
AU - Mautz, Brian S.
AU - Akwo, Elvis A.
AU - Sargurupremraj, Muralidharan
AU - Debette, Stéphanie
AU - Boehnke, Michael
AU - Scott, Laura J.
AU - Luan, Jian’an
AU - Zhao, Jing Hua
AU - Willems, Sara M.
AU - Thériault, Sébastien
AU - Shah, Nabi
AU - Oldmeadow, Christopher
AU - Almgren, Peter
AU - Li-Gao, Ruifang
AU - Verweij, Niek
AU - Boutin, Thibaud S.
AU - Mangino, Massimo
AU - Ntalla, Ioanna
AU - Feofanova, Elena
AU - Surendran, Praveen
AU - Cook, James P.
AU - Karthikeyan, Savita
AU - Lahrouchi, Najim
AU - Liu, Chunyu
AU - Sepúlveda, Nuno
AU - Richardson, Tom G.
AU - Kraja, Aldi
N1 - Funding Information:
P.S. received support from Pfizer Inc. N.P. has received financial support from several pharmaceutical companies which manufacture blood pressurelowering agents, for consultancy fees (Servier), research projects and staff (Servier, Pfizer) and for arranging and speaking at educational meetings (AstraZeneca, Lri Therapharma, Napi, Servier and Pfizer). He holds no stocks and shares in any such companies. M.J.C. is Chief Scientist for Genomics England, a UK Government company. B.M.P. serves on the Data Safety Monitoring Board of a clinical trial funded by Zoll LifeCor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. D.M.K. works as a parttime clinical research consultant for Metabolon, Inc. R.A.S. is an employee and shareholder in GlaxoSmithKline plc. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung and Blood Institute (US); the National Institutes of Health (US); National Health Service (UK); National Institute for Health Research (UK); The Department of Health and Social Care (UK); the EC; or the US Department of Health and Human Services. This publication does not represent the views of the Department of Veterans Affairs or the United States government.
Publisher Copyright:
© 2018, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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.
AB - 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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U2 - 10.1038/s41588-018-0303-9
DO - 10.1038/s41588-018-0303-9
M3 - Article
C2 - 30578418
AN - SCOPUS:85058906993
VL - 51
SP - 51
EP - 62
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 1
ER -