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

In this trans-ethnic multi-omic study we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenome, and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in GWASs of systolic, diastolic and puls...

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Autores principales: 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, Jing-Hua, Zhao, 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., Laakso, Markku, Zeggini, Eleftheria, Sever, Peter, Scott, Robert A., Langenberg, Claudia, Wareham, Nicholas J., Conen, David, Alexander Palmer, Colin Neil, Attia, John, Chasman, Daniel I., Ridker, Paul M., Melander, Olle, Mook-Kanamori, Dennis Owen, van der Harst, Pim, Cucca, Francesco, Schlessinger, David, Hayward, Caroline, Spector, Tim D., Marjo-Riitta, Jarvelin, Hennig, Branwen J., Timpson, Nicholas J., Wei-Qi, Wei, Smith, Joshua C., Xu, Yaomin, Matheny, Michael E., Siew, Edward E., Lindgren, Cecilia, Karl-Heinz, Herzig, Dedoussis, George, Denny, Joshua C., Psaty, Bruce M., Howson, Joanna M. M., Munroe, Patricia B., Newton-Cheh, Christopher, Caulfield, Mark J., Elliott, Paul, Gaziano, J. Michael, Concato, John, Wilson, Peter W.F., Tsao, Philip S., Velez Edwards, Digna R., Susztak, Katalin, O’Donnell, Christopher J., Hung, Adriana M., Edwards, Todd L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2018
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6365102/
https://www.ncbi.nlm.nih.gov/pubmed/30578418
http://dx.doi.org/10.1038/s41588-018-0303-9
Descripción
Sumario:In this trans-ethnic multi-omic study we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenome, and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in GWASs 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 murine renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.

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