Liu Chunyu, Kraja Aldi T, Smith Jennifer A, 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, Surendran Praveen, Drenos Fotios, Cook James P, Auer Paul L, Chu Audrey Y, Giri Ayush, Zhao Wei, Jakobsdottir Johanna, Lin Li-An, Stafford Jeanette M, Amin Najaf, Mei Hao, Yao Jie, Voorman Arend, Larson Martin G, Grove Megan L, Smith Albert V, Hwang Shih-Jen, Chen Han, Huan Tianxiao, Kosova Gulum, Stitziel Nathan O, Kathiresan Sekar, Samani Nilesh, Schunkert Heribert, Deloukas Panos, Li Man, Fuchsberger Christian, Pattaro Cristian, Gorski Mathias, Kooperberg Charles, Papanicolaou George J, Rossouw Jacques E, Faul Jessica D, Kardia Sharon L R, 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, Correa Adolfo, Weir David R, Völker Uwe, Ridker Paul M, Boerwinkle Eric, Gudnason Vilmundur, Reiner Alexander P, van Duijn Cornelia M, Borecki Ingrid B, Edwards Todd L, Chakravarti Aravinda, Rotter Jerome I, Psaty Bruce M, Loos Ruth J F, Fornage Myriam, Ehret Georg B, Newton-Cheh Christopher, Levy Daniel, Chasman Daniel I
Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, Massachusetts, USA.
Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, USA.
Nat Genet. 2016 Oct;48(10):1162-70. doi: 10.1038/ng.3660. Epub 2016 Sep 12.
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.
利用以外显子为中心的单变体和基于基因的检测方法对血压关联结果进行的荟萃分析，在146,562名个体的发现阶段确定了31个新位点，并在另外180,726名个体中进行了随访和荟萃分析（总计n = 327,288）。这些与血压相关的位点富含已知的心血管代谢性状变体。在三个基因NPR1、DBH和PTPMT1中，还观察到罕见和低频错义变体的聚集与血压有关联。此外，在39个先前报道的位点也证实了与血压的关联。所确定的变体涉及与心血管代谢性状、血管功能和发育相关的生物学途径。推断有几个新变体在转录中起作用或在蛋白质-蛋白质相互作用网络中作为枢纽。由所确定的变体构建的遗传风险评分与冠心病和心肌梗死密切相关。这一大组与血压相关的位点提示了高血压的新治疗策略，强调了与心血管代谢风险的联系。
