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

Understanding Society Scientific Group, Ayush Giri, Jacklyn N. Hellwege, Jacob M. Keaton, Jihwan Park, Chengxiang Qiu, Helen R. Warren, Eric S. Torstenson, Csaba P. Kovesdy, 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 WangEvangelos Evangelou, 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 S. Boutin, Massimo Mangino, Ioanna Ntalla, Elena Feofanova, Praveen Surendran, James P. Cook, Savita Karthikeyan, Najim Lahrouchi, Chunyu Liu, Nuno Sepúlveda, Colin Neil Alexander Palmer, Peter W. F. Wilson, Adriana M. Hung, Todd L. Edwards

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Abstract

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.

Original languageEnglish
Pages (from-to)51-62
Number of pages12
JournalNature Genetics
Volume51
Issue number1
Early online date21 Dec 2018
DOIs
Publication statusPublished - Jan 2019

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