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 Wang & 33 others Evangelos 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

Research output: Contribution to journalArticle

3 Citations (Scopus)
99 Downloads (Pure)

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

Fingerprint

Blood Pressure
Veterans
Kidney Tubules
Genes
RNA Sequence Analysis
Genome-Wide Association Study
Transcriptome
Single Nucleotide Polymorphism
Homeostasis
Kidney
Gene Expression

Cite this

Understanding Society Scientific Group, Giri, A., Hellwege, J. N., Keaton, J. M., Park, J., Qiu, C., ... Edwards, T. L. (2019). Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nature Genetics, 51(1), 51-62. https://doi.org/10.1038/s41588-018-0303-9
Understanding Society Scientific Group ; 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. ; 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 ; Palmer, Colin Neil Alexander ; Wilson, Peter W. F. ; Hung, Adriana M. ; Edwards, Todd L. / Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. In: Nature Genetics. 2019 ; Vol. 51, No. 1. pp. 51-62.
@article{3c56a5ea32084e65a48678ac552fac32,
title = "Trans-ethnic association study of blood pressure determinants in over 750,000 individuals",
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.",
author = "{Understanding Society Scientific Group} and Ayush Giri and Hellwege, {Jacklyn N.} and Keaton, {Jacob M.} and Jihwan Park and Chengxiang Qiu and Warren, {Helen R.} and Torstenson, {Eric S.} and Kovesdy, {Csaba P.} and Sun, {Yan V.} and Wilson, {Otis D.} and Cassianne Robinson-Cohen and Roumie, {Christianne L.} and Chung, {Cecilia P.} and Birdwell, {Kelly A.} and Damrauer, {Scott M.} and DuVall, {Scott L.} and Derek Klarin and Kelly Cho and Yu Wang and Evangelos Evangelou and Cabrera, {Claudia P.} and Wain, {Louise V.} and Rojesh Shrestha and Mautz, {Brian S.} and Akwo, {Elvis A.} and Muralidharan Sargurupremraj and St{\'e}phanie Debette and Michael Boehnke and Scott, {Laura J.} and Jian'an Luan and Jing-Hua Zhao and Willems, {Sara M.} and S{\'e}bastien Th{\'e}riault and Nabi Shah and Christopher Oldmeadow and Peter Almgren and Ruifang Li-Gao and Niek Verweij and Boutin, {Thibaud S.} and Massimo Mangino and Ioanna Ntalla and Elena Feofanova and Praveen Surendran and Cook, {James P.} and Savita Karthikeyan and Najim Lahrouchi and Chunyu Liu and Nuno Sep{\'u}lveda and Palmer, {Colin Neil Alexander} and Wilson, {Peter W. F.} and Hung, {Adriana M.} and Edwards, {Todd L.}",
year = "2019",
month = "1",
doi = "10.1038/s41588-018-0303-9",
language = "English",
volume = "51",
pages = "51--62",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "1",

}

Understanding Society Scientific Group, Giri, A, Hellwege, JN, Keaton, JM, Park, J, Qiu, C, Warren, HR, Torstenson, ES, Kovesdy, CP, Sun, YV, Wilson, OD, Robinson-Cohen, C, Roumie, CL, Chung, CP, Birdwell, KA, Damrauer, SM, DuVall, SL, Klarin, D, Cho, K, Wang, Y, Evangelou, E, Cabrera, CP, Wain, LV, Shrestha, R, Mautz, BS, Akwo, EA, Sargurupremraj, M, Debette, S, Boehnke, M, Scott, LJ, Luan, J, Zhao, J-H, Willems, SM, Thériault, S, Shah, N, Oldmeadow, C, Almgren, P, Li-Gao, R, Verweij, N, Boutin, TS, Mangino, M, Ntalla, I, Feofanova, E, Surendran, P, Cook, JP, Karthikeyan, S, Lahrouchi, N, Liu, C, Sepúlveda, N, Palmer, CNA, Wilson, PWF, Hung, AM & Edwards, TL 2019, 'Trans-ethnic association study of blood pressure determinants in over 750,000 individuals', Nature Genetics, vol. 51, no. 1, pp. 51-62. https://doi.org/10.1038/s41588-018-0303-9

Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. / Understanding Society Scientific Group; 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.; 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; Palmer, Colin Neil Alexander; Wilson, Peter W. F.; Hung, Adriana M. (Lead / Corresponding author); Edwards, Todd L. (Lead / Corresponding author).

In: Nature Genetics, Vol. 51, No. 1, 01.2019, p. 51-62.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Trans-ethnic association study of blood pressure determinants in over 750,000 individuals

AU - Understanding Society Scientific Group

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 - Palmer, Colin Neil Alexander

AU - Wilson, Peter W. F.

AU - Hung, Adriana M.

AU - Edwards, Todd L.

PY - 2019/1

Y1 - 2019/1

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.

UR - http://www.scopus.com/inward/record.url?scp=85058906993&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0303-9

DO - 10.1038/s41588-018-0303-9

M3 - Article

VL - 51

SP - 51

EP - 62

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 1

ER -

Understanding Society Scientific Group, Giri A, Hellwege JN, Keaton JM, Park J, Qiu C et al. Trans-ethnic association study of blood pressure determinants in over 750,000 individuals. Nature Genetics. 2019 Jan;51(1):51-62. https://doi.org/10.1038/s41588-018-0303-9