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

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

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.