Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci
Creators: name: Psaty, Bruce M.
name: Daw, E Warwick
name: Raffel, Leslie J.
name: Lin, Li-An
name: Völzke, Henry
name: Fornage, Myriam
name: Jakobsdottir, Johanna
name: O'Donnell, Christopher J.
name: Palmas, Walter
name: Morrison, Alanna C.
name: Kardia, Sharon L. R.
name: Bis, Joshua C.
name: Borecki, Ingrid B.
name: Lu, Yingchang
name: Felix, Stephan B.
name: Pattaro, Cristian
name: Chasman, Daniel I.
name: Loos, Ruth J. F.
name: Amin, Najaf
name: Stafford, Jeanette M.
name: Dörr, Marcus
name: Voorman, Arend
name: Giulianini, Franco
name: Deloukas, Panos
name: Franceschini, Nora
name: Auer, Paul L.
name: Völker, Uwe
name: Launer, Lenore J.
name: Papanicolaou, George J.
name: Edwards, Todd L.
name: Kraja, Aldi T.
name: Liu, Yongmei
name: Van Duijn, Cornelia M.
name: Harris, Tamara B.
name: Lee, Wen-Jane
name: Brody, Jennifer A.
name: Bottinger, Erwin P.
name: Martin, Lisa W.
name: Rossouw, Jacques E.
name: Rettig, Rainer
name: Kosova, Gulum
name: Tsosie, Krystal S.
name: Ridker, Paul M.
name: Chen, Han
name: Levy, Daniel
name: Stitziel, Nathan O.
name: Correa, Adolfo
name: Larson, Martin G.
name: Lee, I-Te
name: Weiss, Stefan
name: Rice, Kenneth
name: Uitterlinden, André G.
name: Gorski, Mathias
name: Li, Man
name: Chu, Audrey Y.
name: Yao, Jie
name: Surendran, Praveen
name: Chen, Yii-Der Ida
name: Liu, Kiang
name: Franco, Oscar H.
name: Faul, Jessica D.
name: Mei, Hao
name: Bouchard, Claude
name: Ehret, Georg B.
name: Samani, Nilesh
name: Hwang, Shih-Jen
name: Liu, Chunyu
name: Grove, Megan L.
name: Sheu, Wayne H.-H.
name: Drenos, Fotios
name: Weir, David R.
name: Schunkert, Heribert
name: Cook, James P.
name: Gudnason, Vilmundur
name: Boerwinkle, Eric
name: Kathiresan, Sekar
name: Newton-Cheh, Christopher
name: Smith, Jennifer A.
name: Salfati, Elias
name: Rotter, Jerome I.
name: Zhao, Wei
name: Edwards, Digna R. Velez
name: Reiner, Alexander P.
name: Taylor, Kent D.
name: Kooperberg, Charles
name: Ganesh, Santhi
name: Giri, Ayush
name: Chakravarti, Aravinda
name: Smith, Albert V.
name: Guo, Xiuqing
name: Gottesman, Omri
name: Huan, Tianxiao
name: Fuchsberger, Christian
name: Kim, Eric
name: Vasan, Ramachandran S.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: Meta-analyses of association results for blood pressure using exome-centric single-variants and gene-based tests identified 31 novel loci in discovery among 146,562 individuals with follow-up and meta-analysis in 180,726 additional individuals (Ntotal=327,288). These blood pressure loci are enriched for known cardiometabolic trait variants. Associations were also observed for the aggregation of rare/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 loci suggests new therapeutic strategies for hypertension emphasizing a link with cardiometabolic risk.