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Title

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

Authors
Liu, Chunyu
Kraja, Aldi T
Smith, Jennifer A
Brody, Jennifer A
Franceschini, Nora
Newton-Cheh, Christopher
Levy, Daniel
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Published in Nature Genetics. 2016, vol. 48, no. 10, p. 1162-1170
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.
Keywords Blood Pressure/geneticsExomeGenetic VariationGenomeHumanGenome-Wide Association StudyGenotypeHumansHypertension/geneticsOligonucleotide Array Sequence AnalysisPolymorphismSingle Nucleotide
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PMID: 27618448
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Article (Published version) (935 Kb) - document accessible for UNIGE members only Limited access to UNIGE
Other version: https://www.nature.com/articles/ng.3660
Structures
Research group Traits génétiques complexes (901)
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LIU, Chunyu et al. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. In: Nature Genetics, 2016, vol. 48, n° 10, p. 1162-1170. doi: 10.1038/ng.3660 https://archive-ouverte.unige.ch/unige:127748

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Deposited on : 2019-12-10

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