MVP_BP_Main_Manuscript_08272018.pdf (2.91 MB)
Trans-ethnic association study of blood pressure determinants in over 750,000 individuals
journal contribution
posted on 2019-04-11, 10:37 authored by A Giri, JN Hellwege, JM Keaton, J Park, C Qiu, HR Warren, ES Torstenson, CP Kovesdy, YV Sun, OD Wilson, C Robinson-Cohen, PB Munroe, C Newton-Cheh, MJ Caulfield, P Elliott, JM Gaziano, J Concato, PWF Wilson, PS Tsao, DR Velez Edwards, K Susztak, Million Veteran Program, CJ O'Donnell, AM Hung, TL Edwards, CL Roumie, CP Chung, KA Birdwell, SM Damrauer, SL DuVall, D Klarin, K Cho, Y Wang, E Evangelou, CP Cabrera, LV Wain, R Shrestha, BS Mautz, EA Akwo, M Sargurupremraj, S Debette, M Boehnke, LJ Scott, J Luan, J-H Zhao, SM Willems, S Thériault, N Shah, C Oldmeadow, P Almgren, R Li-Gao, N Verweij, TS Boutin, M Mangino, I Ntalla, E Feofanova, P Surendran, JP Cook, S Karthikeyan, N Lahrouchi, C Liu, N Sepúlveda, TG Richardson, A Kraja, P Amouyel, M Farrall, NR Poulter, Understanding Society Scientific Group, International Consortium for Blood Pressure, Blood Pressure-International Consortium of Exome Chip Studies, M Laakso, E Zeggini, P Sever, RA Scott, C Langenberg, NJ Wareham, D Conen, CNA Palmer, J Attia, DI Chasman, PM Ridker, O Melander, DO Mook-Kanamori, PVD Harst, F Cucca, D Schlessinger, C Hayward, TD Spector, M-R Jarvelin, BJ Hennig, NJ Timpson, W-Q Wei, JC Smith, Y Xu, ME Matheny, EE Siew, C Lindgren, K-H Herzig, G Dedoussis, JC Denny, BM Psaty, JMM HowsonIn 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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Nat Genet, 2019, 51 (1), pp. 51-62Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Health SciencesVersion
- AM (Accepted Manuscript)
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Nat GenetPublisher
Nature Research (part of Springer Nature)eissn
1546-1718Acceptance date
2018-10-31Copyright date
2018Available date
2019-06-21Publisher DOI
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https://www.nature.com/articles/s41588-018-0303-9Notes
The file associated with this record is under embargo until 6 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.Language
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