TY - JOUR T1 - Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. JF - Nat Genet Y1 - 2016 A1 - Liu, Chunyu A1 - Kraja, Aldi T A1 - Jennifer A Smith A1 - Brody, Jennifer A A1 - Franceschini, Nora A1 - Joshua C. Bis A1 - Kenneth Rice A1 - Alanna C Morrison A1 - Lu, Yingchang A1 - Weiss, Stefan A1 - Guo, Xiuqing A1 - Walter R Palmas A1 - Martin, Lisa W A1 - Yii-Der I Chen A1 - Surendran, Praveen A1 - Drenos, Fotios A1 - Cook, James P A1 - Auer, Paul L A1 - Chu, Audrey Y A1 - Giri, Ayush A1 - Wei Zhao A1 - Jakobsdottir, Johanna A1 - Lin, Li-An A1 - Stafford, Jeanette M A1 - Amin, Najaf A1 - Mei, Hao A1 - Yao, Jie A1 - Voorman, Arend A1 - Larson, Martin G A1 - Grove, Megan L A1 - Albert Vernon Smith A1 - Hwang, Shih-Jen A1 - Chen, Han A1 - Huan, Tianxiao A1 - Kosova, Gulum A1 - Stitziel, Nathan O A1 - Kathiresan, Sekar A1 - Nilesh J Samani A1 - Schunkert, Heribert A1 - Deloukas, Panos A1 - Li, Man A1 - Fuchsberger, Christian A1 - Pattaro, Cristian A1 - Gorski, Mathias A1 - Charles Kooperberg A1 - George J Papanicolaou A1 - Rossouw, Jacques E A1 - Jessica Faul A1 - Sharon L R Kardia A1 - Bouchard, Claude A1 - Raffel, Leslie J A1 - André G Uitterlinden A1 - Franco, Oscar H A1 - Ramachandran S Vasan A1 - O'Donnell, Christopher J A1 - Kent D Taylor A1 - Liu, Kiang A1 - Erwin P Bottinger A1 - Gottesman, Omri A1 - Daw, E Warwick A1 - Giulianini, Franco A1 - Ganesh, Santhi A1 - Salfati, Elias A1 - Tamara B Harris A1 - Lenore J Launer A1 - Dörr, Marcus A1 - Felix, Stephan B A1 - Rettig, Rainer A1 - Völzke, Henry A1 - Eric S Kim A1 - Lee, Wen-Jane A1 - Lee, I-Te A1 - Sheu, Wayne H-H A1 - Tsosie, Krystal S A1 - Digna R Velez Edwards A1 - Yongmei Liu A1 - Correa, Adolfo A1 - David R Weir A1 - Völker, Uwe A1 - Ridker, Paul M A1 - Boerwinkle, Eric A1 - Gudnason, Vilmundur A1 - Reiner, Alexander P A1 - Cornelia M van Duijn A1 - Ingrid B Borecki A1 - Edwards, Todd L A1 - Chakravarti, Aravinda A1 - Rotter, Jerome I A1 - Psaty, Bruce M A1 - Ruth J F Loos A1 - Myriam Fornage A1 - Georg B Ehret A1 - Newton-Cheh, Christopher A1 - Levy, Daniel A1 - Daniel I Chasman AB -

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.

VL - 48 IS - 10 ER -