Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-10

AUTHORS

Chunyu Liu, Aldi T Kraja, Jennifer A Smith, Jennifer A Brody, Nora Franceschini, Joshua C Bis, Kenneth Rice, Alanna C Morrison, Yingchang Lu, Stefan Weiss, Xiuqing Guo, Walter Palmas, Lisa W Martin, Yii-Der Ida Chen, Praveen Surendran, Fotios Drenos, James P Cook, Paul L Auer, Audrey Y Chu, Ayush Giri, Wei Zhao, Johanna Jakobsdottir, Li-An Lin, Jeanette M Stafford, Najaf Amin, Hao Mei, Jie Yao, Arend Voorman, CHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D-GENES Consortium, Martin G Larson, Megan L Grove, Albert V Smith, Shih-Jen Hwang, Han Chen, Tianxiao Huan, Gulum Kosova, Nathan O Stitziel, Sekar Kathiresan, Nilesh Samani, Heribert Schunkert, Panos Deloukas, Myocardial Infarction Genetics and CAIoGRAM Exome Consortia, Man Li, Christian Fuchsberger, Cristian Pattaro, Mathias Gorski, CKDGen Consortium, Charles Kooperberg, George J Papanicolaou, Jacques E Rossouw, Jessica D Faul, Sharon L R Kardia, Claude Bouchard, Leslie J Raffel, André G Uitterlinden, Oscar H Franco, Ramachandran S Vasan, Christopher J O'Donnell, Kent D Taylor, Kiang Liu, Erwin P Bottinger, Omri Gottesman, E Warwick Daw, Franco Giulianini, Santhi Ganesh, Elias Salfati, Tamara B Harris, Lenore J Launer, Marcus Dörr, Stephan B Felix, Rainer Rettig, Henry Völzke, Eric Kim, Wen-Jane Lee, I-Te Lee, Wayne H-H Sheu, Krystal S Tsosie, Digna R Velez Edwards, Yongmei Liu, Adolfo Correa, David R Weir, Uwe Völker, Paul M Ridker, Eric Boerwinkle, Vilmundur Gudnason, Alexander P Reiner, Cornelia M van Duijn, Ingrid B Borecki, Todd L Edwards, Aravinda Chakravarti, Jerome I Rotter, Bruce M Psaty, Ruth J F Loos, Myriam Fornage, Georg B Ehret, Christopher Newton-Cheh, Daniel Levy, Daniel I Chasman

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. More... »

PAGES

1162-1170

References to SciGraph publications

Journal

TITLE

Nature Genetics

ISSUE

10

VOLUME

48

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng.3660

DOI

http://dx.doi.org/10.1038/ng.3660

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049121823

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27618448


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