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

Publication ,  Journal Article
Liu, C; Kraja, AT; Smith, JA; Brody, JA; Franceschini, N; Bis, JC; Rice, K; Morrison, AC; Lu, Y; Weiss, S; Guo, X; Palmas, W; Martin, LW ...
Published in: Nat Genet
October 2016

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.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2016

Volume

48

Issue

10

Start / End Page

1162 / 1170

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Hypertension
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genome, Human
  • Genetic Variation
  • Exome
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Liu, C., Kraja, A. T., Smith, J. A., Brody, J. A., Franceschini, N., Bis, J. C., … Chasman, D. I. (2016). Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. Nat Genet, 48(10), 1162–1170. https://doi.org/10.1038/ng.3660
Liu, Chunyu, Aldi T. Kraja, Jennifer A. Smith, Jennifer A. Brody, Nora Franceschini, Joshua C. Bis, Kenneth Rice, et al. “Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.Nat Genet 48, no. 10 (October 2016): 1162–70. https://doi.org/10.1038/ng.3660.
Liu C, Kraja AT, Smith JA, Brody JA, Franceschini N, Bis JC, et al. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. Nat Genet. 2016 Oct;48(10):1162–70.
Liu, Chunyu, et al. “Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.Nat Genet, vol. 48, no. 10, Oct. 2016, pp. 1162–70. Pubmed, doi:10.1038/ng.3660.
Liu C, Kraja AT, Smith JA, Brody JA, Franceschini N, Bis JC, Rice K, Morrison AC, Lu Y, Weiss S, Guo X, Palmas W, Martin LW, Chen Y-DI, Surendran P, Drenos F, Cook JP, Auer PL, Chu AY, Giri A, Zhao W, Jakobsdottir J, Lin L-A, Stafford JM, Amin N, Mei H, Yao J, Voorman A, CHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D-GENES Consortium, Larson MG, Grove ML, Smith AV, Hwang S-J, Chen H, Huan T, Kosova G, Stitziel NO, Kathiresan S, Samani N, Schunkert H, Deloukas P, Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia, Li M, Fuchsberger C, Pattaro C, Gorski M, CKDGen Consortium, Kooperberg C, Papanicolaou GJ, Rossouw JE, Faul JD, Kardia SLR, Bouchard C, Raffel LJ, Uitterlinden AG, Franco OH, Vasan RS, O’Donnell CJ, Taylor KD, Liu K, Bottinger EP, Gottesman O, Daw EW, Giulianini F, Ganesh S, Salfati E, Harris TB, Launer LJ, Dörr M, Felix SB, Rettig R, Völzke H, Kim E, Lee W-J, Lee I-T, Sheu WH-H, Tsosie KS, Edwards DRV, Liu Y, Correa A, Weir DR, Völker U, Ridker PM, Boerwinkle E, Gudnason V, Reiner AP, van Duijn CM, Borecki IB, Edwards TL, Chakravarti A, Rotter JI, Psaty BM, Loos RJF, Fornage M, Ehret GB, Newton-Cheh C, Levy D, Chasman DI. Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci. Nat Genet. 2016 Oct;48(10):1162–1170.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

October 2016

Volume

48

Issue

10

Start / End Page

1162 / 1170

Location

United States

Related Subject Headings

  • Polymorphism, Single Nucleotide
  • Oligonucleotide Array Sequence Analysis
  • Hypertension
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genome, Human
  • Genetic Variation
  • Exome
  • Developmental Biology