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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals.
Tuesday,2018-01-16 18:19 America/Los_Angeles — ecterry
| Title | New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475 000 Individuals. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Kraja, AT, Cook, JP, Warren, HR, Surendran, P, Liu, C, Evangelou, E, Manning, AK, Grarup, N, Drenos, F, Sim, X, Smith, AVernon, Amin, N, Blakemore, AIF, Bork-Jensen, J, Brandslund, I, Farmaki, A-E, Fava, C, Ferreira, T, Herzig, K-H, Giri, A, Giulianini, F, Grove, ML, Guo, X, Harris, SE, Have, CT, Havulinna, AS, Zhang, H, Jørgensen, ME, Käräjämäki, AM, Kooperberg, C, Linneberg, A, Little, L, Liu, Y, Bonnycastle, LL, Lu, Y, Mägi, R, Mahajan, A, Malerba, G, Marioni, RE, Mei, H, Menni, C, Morrison, AC, Padmanabhan, S, Palmas, W, Poveda, A, Rauramaa, R, Rayner, NWilliam, Riaz, M, Rice, K, Richard, MA, Smith, JA, Southam, L, Stančáková, A, Stirrups, KE, Tragante, V, Tuomi, T, Tzoulaki, I, Varga, TV, Weiss, S, Yiorkas, AM, Young, R, Zhang, W, Barnes, MR, Cabrera, CP, Gao, H, Boehnke, M, Boerwinkle, E, Chambers, JC, Connell, JM, Christensen, CK, de Boer, RA, Deary, IJ, Dedoussis, G, Deloukas, P, Dominiczak, AF, Dörr, M, Joehanes, R, Edwards, TL, Esko, T, Fornage, M, Franceschini, N, Franks, PW, Gambaro, G, Groop, L, Hallmans, G, Hansen, T, Hayward, C, Heikki, O, Ingelsson, E, Tuomilehto, J, Jarvelin, M-R, Kardia, SLR, Karpe, F, Kooner, JS, Lakka, TA, Langenberg, C, Lind, L, Loos, RJF, Laakso, M, McCarthy, MI, Melander, O, Mohlke, KL, Morris, AP, Palmer, CNA, Pedersen, O, Polasek, O, Poulter, NR, Province, MA, Psaty, BM, Ridker, PM, Rotter, JI, Rudan, I, Salomaa, V, Samani, NJ, Sever, PJ, Skaaby, T, Stafford, JM, Starr, JM, van der Harst, P, van der Meer, P, van Duijn, CM, Vergnaud, A-C, Gudnason, V, Wareham, NJ, Wilson, JG, Willer, CJ, Witte, DR, Zeggini, E, Saleheen, D, Butterworth, AS, Danesh, J, Asselbergs, FW, Wain, LV, Ehret, GB, Chasman, DI, Caulfield, MJ, Elliott, P, Lindgren, CM, Levy, D, Newton-Cheh, C, Munroe, PB, Howson, JMM |
| Corporate/Institutional Authors | Understanding Society Scientific Group, CHARGE EXOME BP, CHD Exome+, Exome BP, GoT2D:T2DGenes Consortia, The UK Biobank Cardio-Metabolic Traits Consortium Blood Pressure Working Group† |
| Journal | Circ Cardiovasc Genet |
| Volume | 10 |
| Issue | 5 |
| Date Published | 2017 Oct |
| ISSN | 1942-3268 |
| Abstract | <p><b>BACKGROUND: </b>Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.</p><p><b>METHODS AND RESULTS: </b>Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, ≈475 000), and the other in the subset of individuals of European descent (≈423 000). Twenty-one SNVs were genome-wide significant (P<5×10-8) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.</p><p><b>CONCLUSIONS: </b>We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.</p> |
| DOI | 10.1161/CIRCGENETICS.117.001778 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 29030403 |
| Grant List | R01 DK093757 / DK / NIDDK NIH HHS / United States U01 DK085501 / DK / NIDDK NIH HHS / United States R01 DK078616 / DK / NIDDK NIH HHS / United States RC4 AG039029 / AG / NIA NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States R01 HL103612 / HL / NHLBI NIH HHS / United States R03 AG046389 / AG / NIA NIH HHS / United States N01 HC085081 / HC / NHLBI NIH HHS / United States R01 HL071259 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States N01 AG062101 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States R01 HL071252 / HL / NHLBI NIH HHS / United States R01 HL043851 / HL / NHLBI NIH HHS / United States N01 HC085083 / HC / NHLBI NIH HHS / United States R01 DK072193 / DK / NIDDK NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States R01 HL071250 / HL / NHLBI NIH HHS / United States N01 HC095164 / HC / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States N01 HC095166 / HC / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States N01 AG062106 / AG / NIA NIH HHS / United States N01 HC095160 / HC / NHLBI NIH HHS / United States R01 HL093029 / HL / NHLBI NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States N01 HC085082 / HC / NHLBI NIH HHS / United States U01 HG004729 / HG / NHGRI NIH HHS / United States N01 HC085080 / HC / NHLBI NIH HHS / United States K24 DK080140 / DK / NIDDK NIH HHS / United States U01 DK062370 / DK / NIDDK NIH HHS / United States N01 HC095165 / HC / NHLBI NIH HHS / United States R21 HL123677 / HL / NHLBI NIH HHS / United States R01 HL080467 / HL / NHLBI NIH HHS / United States R01 HL071205 / HL / NHLBI NIH HHS / United States UL1 TR000040 / TR / NCATS NIH HHS / United States RC2 AG036495 / AG / NIA NIH HHS / United States N01 HC095163 / HC / NHLBI NIH HHS / United States RL1 MH083268 / MH / NIMH NIH HHS / United States R01 HL117078 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 HL071258 / HL / NHLBI NIH HHS / United States N01 HC095159 / HC / NHLBI NIH HHS / United States |
ePub date:
17/10