Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.
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Authors
Liu, Chunyu
Kraja, Aldi T
Brody, Jennifer A
Franceschini, Nora
Bis, Joshua C
Rice, Kenneth
Morrison, Alanna C
Lu, Yingchang
Weiss, Stefan
Guo, Xiuqing
Palmas, Walter
Martin, Lisa W
Chen, Yii-Der Ida
Drenos, Fotios
Cook, James P
Auer, Paul L
Chu, Audrey Y
Giri, Ayush
Zhao, Wei
Jakobsdottir, Johanna
Stafford, Jeanette M
Amin, Najaf
Mei, Hao
Yao, Jie
Voorman, Arend
CHD Exome+ Consortium
ExomeBP Consortium
GoT2DGenes Consortium
T2D-GENES Consortium
Larson, Martin G
Grove, Megan L
Hwang, Shih-Jen
Huan, Tianxiao
Kosova, Gulum
Stitziel, Nathan O
Kathiresan, Sekar
Samani, Nilesh
Schunkert, Heribert
Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia
Fuchsberger, Christian
Pattaro, Cristian
Gorski, Mathias
CKDGen Consortium
Kooperberg, Charles
Papanicolaou, George J
Rossouw, Jacques E
Faul, Jessica D
Kardia, Sharon LR
Bouchard, Claude
Raffel, Leslie J
Uitterlinden, André G
Franco, Oscar H
Vasan, Ramachandran S
O'Donnell, Christopher J
Taylor, Kent D
Liu, Kiang
Bottinger, Erwin P
Gottesman, Omri
Daw, E Warwick
Giulianini, Franco
Ganesh, Santhi
Salfati, Elias
Harris, Tamara B
Launer, Lenore J
Dörr, Marcus
Felix, Stephan B
Rettig, Rainer
Völzke, Henry
Kim, Eric
Lee, Wen-Jane
Lee, I-Te
Sheu, Wayne H-H
Tsosie, Krystal S
Edwards, Digna R Velez
Liu, Yongmei
Weir, David R
Völker, Uwe
Ridker, Paul M
Boerwinkle, Eric
Gudnason, Vilmundur
Reiner, Alexander P
van Duijn, Cornelia M
Borecki, Ingrid B
Chakravarti, Aravinda
Rotter, Jerome I
Psaty, Bruce M
Loos, Ruth JF
Fornage, Myriam
Newton-Cheh, Christopher
Levy, Daniel
Chasman, Daniel I
Publication Date
2016-10Journal Title
Nat Genet
ISSN
1061-4036
Publisher
Springer Science and Business Media LLC
Volume
48
Issue
10
Pages
1162-1170
Language
eng
Type
Article
This Version
AM
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Liu, C., Kraja, A. T., Smith, J. A., Brody, J. A., Franceschini, N., Bis, J. C., Rice, K., et al. (2016). Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.. Nat Genet, 48 (10), 1162-1170. https://doi.org/10.1038/ng.3660
Abstract
Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
Keywords
CHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D-GENES Consortium, Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia, CKDGen Consortium, Humans, Hypertension, Oligonucleotide Array Sequence Analysis, Blood Pressure, Genotype, Polymorphism, Single Nucleotide, Genome, Human, Genetic Variation, Genome-Wide Association Study, Exome
Sponsorship
Medical Research Council (MR/L003120/1)
Medical Research Council (G0800270)
British Heart Foundation (None)
British Heart Foundation (None)
Identifiers
External DOI: https://doi.org/10.1038/ng.3660
This record's URL: https://www.repository.cam.ac.uk/handle/1810/269427
Rights
Licence:
http://www.rioxx.net/licenses/all-rights-reserved
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