@article {7264, title = {Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.}, journal = {Nat Genet}, volume = {48}, year = {2016}, month = {2016 Oct}, pages = {1162-70}, 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.

}, issn = {1546-1718}, doi = {10.1038/ng.3660}, author = {Liu, Chunyu and Kraja, Aldi T and Smith, Jennifer A and Brody, Jennifer A and Franceschini, Nora and Bis, Joshua C and Rice, Kenneth and Morrison, Alanna C and Lu, Yingchang and Weiss, Stefan and Guo, Xiuqing and Palmas, Walter and Martin, Lisa W and Chen, Yii-Der Ida and Surendran, Praveen and Drenos, Fotios and Cook, James P and Auer, Paul L and Chu, Audrey Y and Giri, Ayush and Zhao, Wei and Jakobsdottir, Johanna and Lin, Li-An and Stafford, Jeanette M and Amin, Najaf and Mei, Hao and Yao, Jie and Voorman, Arend and Larson, Martin G and Grove, Megan L and Smith, Albert V and Hwang, Shih-Jen and Chen, Han and Huan, Tianxiao and Kosova, Gulum and Stitziel, Nathan O and Kathiresan, Sekar and Samani, Nilesh and Schunkert, Heribert and Deloukas, Panos and Li, Man and Fuchsberger, Christian and Pattaro, Cristian and Gorski, Mathias and Kooperberg, Charles and Papanicolaou, George J and Rossouw, Jacques E and Faul, Jessica D and Kardia, Sharon L R and Bouchard, Claude and Raffel, Leslie J and Uitterlinden, Andr{\'e} G and Franco, Oscar H and Vasan, Ramachandran S and O{\textquoteright}Donnell, Christopher J and Taylor, Kent D and Liu, Kiang and Bottinger, Erwin P and Gottesman, Omri and Daw, E Warwick and Giulianini, Franco and Ganesh, Santhi and Salfati, Elias and Harris, Tamara B and Launer, Lenore J and D{\"o}rr, Marcus and Felix, Stephan B and Rettig, Rainer and V{\"o}lzke, Henry and Kim, Eric and Lee, Wen-Jane and Lee, I-Te and Sheu, Wayne H-H and Tsosie, Krystal S and Edwards, Digna R Velez and Liu, Yongmei and Correa, Adolfo and Weir, David R and V{\"o}lker, Uwe and Ridker, Paul M and Boerwinkle, Eric and Gudnason, Vilmundur and Reiner, Alexander P and van Duijn, Cornelia M and Borecki, Ingrid B and Edwards, Todd L and Chakravarti, Aravinda and Rotter, Jerome I and Psaty, Bruce M and Loos, Ruth J F and Fornage, Myriam and Ehret, Georg B and Newton-Cheh, Christopher and Levy, Daniel and Chasman, Daniel I} }