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

TitleMeta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.
Publication TypeJournal Article
Year of Publication2016
AuthorsLiu, C, Kraja, AT, Smith, JA, Brody, JA, Franceschini, N, Joshua C. Bis, Rice, K, Morrison, A, 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, Larson, MG, Grove, ML, Smith, AVernon, Hwang, S-J, Chen, H, Huan, T, Kosova, G, Stitziel, NO, Kathiresan, S, Samani, N, Schunkert, H, Deloukas, P, Li, M, Fuchsberger, C, Pattaro, C, Gorski, M, Kooperberg, C, Papanicolaou, GJ, Rossouw, JE, Faul, JD, Kardia, SLR, Bouchard, C, Raffel, LJ, Uitterlinden, AG, Franco, OH, Vasan, RS, O'Donnell, CJ, Taylor, K, Liu, K, Bottinger, EP, Gottesman, O, E Daw, W, Giulianini, F, Ganesh, S, Salfati, E, Harris, TB, Launer, LJ, Dörr, M, Felix, SB, Rettig, R, Völzke, H, Kim, ES, Lee, W-J, Lee, I-T, Sheu, WH-H, Tsosie, KS, Edwards, DRVelez, 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, G, Newton-Cheh, C, Levy, D, Chasman, DI
Corporate AuthorsCHD Exome+ Consortium, ExomeBP Consortium, GoT2DGenes Consortium, T2D-GENES Consortium, Myocardial Infarction Genetics and CARDIoGRAM Exome Consortia, CKDGen Consortium
JournalNat Genet
Volume48
Issue10
Pagination1162-70
Date Published2016 Oct
ISSN Number1546-1718
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.

DOI10.1038/ng.3660
Alternate JournalNat. Genet.
Citation Key8885
PubMed ID27618448
Grant ListRC2 HL102419 / HL / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
R01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL068986 / HL / NHLBI NIH HHS / United States
U01 HL130114 / HL / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
U01 HG004603 / HG / NHGRI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
R01 HL093029 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
R01 HL084099 / HL / NHLBI NIH HHS / United States
RC2 GM092618 / GM / NIGMS NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R21 HL121429 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States