You are here
Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.
Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
| Title | Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Johnson, AD, Chasman, DI, Smith, AV, Tobin, MD, Verwoert, GC, Hwang, S-J, Pihur, V, Vollenweider, P, O'Reilly, PF, Amin, N, Bragg-Gresham, JL, Teumer, A, Glazer, NL, Launer, L, Zhao, JH, Aulchenko, Y, Heath, S, Sõber, S, Parsa, A, Luan, J'an, Arora, P, Dehghan, A, Zhang, F, Lucas, G, Hicks, AA, Jackson, AU, Peden, JF, Tanaka, T, Wild, SH, Rudan, I, Igl, W, Milaneschi, Y, Parker, AN, Fava, C, Chambers, JC, Fox, ER, Kumari, M, Go, MJ, van der Harst, P, Kao, WHL, Sjögren, M, Vinay, DG, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, PH, Liu, Y, Shi, G, Kuusisto, J, Tayo, B, Seielstad, M, Sim, X, Nguyen, K-DH, Lehtimäki, T, Matullo, G, Wu, Y, Gaunt, TR, Onland-Moret, CN, Cooper, MN, Platou, CGP, Org, E, Hardy, R, Dahgam, S, Palmen, J, Vitart, V, Braund, PS, Kuznetsova, T, Uiterwaal, CSPM, Adeyemo, A, Palmas, W, Campbell, H, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, ND, Aspelund, T, Garcia, M, Chang, Y-PC, O'Connell, JR, Steinle, NI, Grobbee, DE, Arking, DE, Kardia, SL, Morrison, AC, Hernandez, D, Najjar, S, McArdle, WL, Hadley, D, Brown, MJ, Connell, JM, Hingorani, AD, Day, INM, Lawlor, DA, Beilby, JP, Lawrence, RW, Clarke, R, Hopewell, JC, Ongen, H, Dreisbach, AW, Li, Y, Young, HJ, Bis, JC, Kähönen, M, Viikari, J, Adair, LS, Lee, NR, Chen, M-H, Olden, M, Pattaro, C, Bolton, JHA, Köttgen, A, Bergmann, S, Mooser, V, Chaturvedi, N, Frayling, TM, Islam, M, Jafar, TH, Erdmann, J, Kulkarni, SR, Bornstein, SR, Grässler, J, Groop, L, Voight, BF, Kettunen, J, Howard, P, Taylor, A, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Barroso, I, Khaw, K-T, Weder, AB, Hunt, SC, Sun, YV, Bergman, RN, Collins, FS, Bonnycastle, LL, Scott, LJ, Stringham, HM, Peltonen, L, Perola, M, Vartiainen, E, Brand, S-M, Staessen, JA, Wang, TJ, Burton, PR, Artigas, MSoler, Dong, Y, Snieder, H, Wang, X, Zhu, H, Lohman, KK, Rudock, ME, Heckbert, SR, Smith, NL, Wiggins, KL, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, CD, Rosengren, A, Thelle, DS, Corsi, AM, Singleton, A, Forrester, T, Hilton, G, McKenzie, CA, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Wichmann, H-E, Cho, YS, Kim, H-L, Lee, J-Y, Scott, J, Sehmi, JS, Zhang, W, Hedblad, B, Nilsson, P, Smith, GD, Wong, A, Narisu, N, Stančáková, A, Raffel, LJ, Yao, J, Kathiresan, S, O'Donnell, CJ, Schwartz, SM, Ikram, AM, Longstreth, WT, Mosley, TH, Seshadri, S, Shrine, NRG, Wain, LV, Morken, MA, Swift, AJ, Laitinen, J, Prokopenko, I, Zitting, P, Cooper, JA, Humphries, SE, Danesh, J, Rasheed, A, Goel, A, Hamsten, A, Watkins, H, Bakker, SJL, van Gilst, WH, Janipalli, CS, Mani, RK, Yajnik, CS, Hofman, A, Mattace-Raso, FUS, Oostra, BA, Demirkan, A, Isaacs, A, Rivadeneira, F, Lakatta, EG, Orrù, M, Scuteri, A, Ala-Korpela, M, Kangas, AJ, Lyytikäinen, L-P, Soininen, P, Tukiainen, T, Würtz, P, Ong, RT-H, Dörr, M, Kroemer, HK, Völker, U, Völzke, H, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Deloukas, P, Mangino, M, Spector, TD, Zhai, G, Meschia, JF, Nalls, MA, Sharma, P, Terzic, J, Kumar, KMV, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, LE, Fowkes, GFR, Charchar, FJ, Schwarz, PEH, Hayward, C, Guo, X, Rotimi, C, Bots, ML, Brand, E, Samani, NJ, Polasek, O, Talmud, PJ, Nyberg, F, Kuh, D, Laan, M, Hveem, K, Palmer, LJ, van der Schouw, YT, Casas, JP, Mohlke, KL, Vineis, P, Raitakari, O, Ganesh, SK, Wong, TY, Tai, SE, Cooper, RS, Laakso, M, Rao, DC, Harris, TB, Morris, RW, Dominiczak, AF, Kivimaki, M, Marmot, MG, Miki, T, Saleheen, D, Chandak, GR, Coresh, J, Navis, G, Salomaa, V, Han, B-G, Zhu, X, Kooner, JS, Melander, O, Ridker, PM, Bandinelli, S, Gyllensten, UB, Wright, AF, Wilson, JF, Ferrucci, L, Farrall, M, Tuomilehto, J, Pramstaller, PP, Elosua, R, Soranzo, N, Sijbrands, EJG, Altshuler, D, Loos, RJF, Shuldiner, AR, Gieger, C, Meneton, P, Uitterlinden, AG, Wareham, NJ, Gudnason, V, Rotter, JI, Rettig, R, Uda, M, Strachan, DP, Witteman, JCM, Hartikainen, A-L, Beckmann, JS, Boerwinkle, E, Vasan, RS, Boehnke, M, Larson, MG, Jarvelin, M-R, Psaty, BM, Abecasis, GR, Chakravarti, A, Elliott, P, van Duijn, CM, Newton-Cheh, C, Levy, D, Caulfield, MJ, Johnson, T |
| Corporate/Institutional Authors | International Consortium for Blood Pressure Genome-Wide Association Studies, CARDIoGRAM consortium, CKDGen Consortium, KidneyGen Consortium, EchoGen consortium, CHARGE-HF consortium |
| Journal | Nature |
| Volume | 478 |
| Issue | 7367 |
| Pagination | 103-9 |
| Date Published | 2011 Sep 11 |
| ISSN | 1476-4687 |
| Keywords | Africa, Asia, Blood Pressure, Cardiovascular Diseases, Coronary Artery Disease, Europe, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Kidney Diseases, Polymorphism, Single Nucleotide, Stroke |
| Abstract | <p>Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention.</p> |
| DOI | 10.1038/nature10405 |
| Alternate Journal | Nature |
| PubMed ID | 21909115 |
| PubMed Central ID | PMC3340926 |
| Grant List | M01-RR00425 / RR / NCRR NIH HHS / United States U01HG004446 / HG / NHGRI NIH HHS / United States N01 HC-95169 / HC / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States DK078150 / DK / NIDDK NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States CZB/4/710 / / Chief Scientist Office / United Kingdom G9521010 / / Medical Research Council / United Kingdom R01HL06094 / HL / NHLBI NIH HHS / United States U01HG004726 / HG / NHGRI NIH HHS / United States U01HG004438 / HG / NHGRI NIH HHS / United States R01 HL088119 / HL / NHLBI NIH HHS / United States N01-HC-95162 / HC / NHLBI NIH HHS / United States G0801056 / / Medical Research Council / United Kingdom 5R01HL08770002 / HL / NHLBI NIH HHS / United States DK075787 / DK / NIDDK NIH HHS / United States HL 54512 / HL / NHLBI NIH HHS / United States P30 ES010126 / ES / NIEHS NIH HHS / United States U01 NS069208-01 / NS / NINDS NIH HHS / United States RG/08/008/25291 / / British Heart Foundation / United Kingdom G0400874 / / Medical Research Council / United Kingdom R01 HL073410 / HL / NHLBI NIH HHS / United States P01CA087969 / CA / NCI NIH HHS / United States 33014 / / PHS HHS / United States HL043851 / HL / NHLBI NIH HHS / United States S06GM008016-380111 / GM / NIGMS NIH HHS / United States G0501942 / / British Heart Foundation / United Kingdom R01 HL087647 / HL / NHLBI NIH HHS / United States R01 HL086694-04A1 / HL / NHLBI NIH HHS / United States TW008288 / TW / FIC NIH HHS / United States G0600705 / / Medical Research Council / United Kingdom MC_UP_A100_1003 / / Medical Research Council / United Kingdom N01-HC-85085 / HC / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States G19/35 / / Medical Research Council / United Kingdom U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL054527 / HL / NHLBI NIH HHS / United States RG/07/005/23633 / / British Heart Foundation / United Kingdom S06GM008016-320107 / GM / NIGMS NIH HHS / United States U01HG004738 / HG / NHGRI NIH HHS / United States SP/04/002 / / British Heart Foundation / United Kingdom G20234 / / Biotechnology and Biological Sciences Research Council / United Kingdom P01CA055075 / CA / NCI NIH HHS / United States N01-AG-1-2109 / AG / NIA NIH HHS / United States R01HL060919 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States K12RR023250 / RR / NCRR NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States U01HG004415 / HG / NHGRI NIH HHS / United States G0100222 / / Medical Research Council / United Kingdom PG97012 / / British Heart Foundation / United Kingdom U54 RR020278 / RR / NCRR NIH HHS / United States U01HG004735 / HG / NHGRI NIH HHS / United States RR-024156 / RR / NCRR NIH HHS / United States MC_U127561128 / / Medical Research Council / United Kingdom R01 CA094143 / CA / NCI NIH HHS / United States N01AG62101 / AG / NIA NIH HHS / United States N01-HC-95163 / HC / NHLBI NIH HHS / United States G0700931 / / Medical Research Council / United Kingdom R01HL061019 / HL / NHLBI NIH HHS / United States 079895 / / Wellcome Trust / United Kingdom N01-HC-55016 / HC / NHLBI NIH HHS / United States N01-HC-95168 / HC / NHLBI NIH HHS / United States 263 MD 821336 / MD / NIMHD NIH HHS / United States HL54512 / HL / NHLBI NIH HHS / United States HL-87660 / HL / NHLBI NIH HHS / United States G9521010D / / Medical Research Council / United Kingdom R01 DK072193 / DK / NIDDK NIH HHS / United States HL086718 / HL / NHLBI NIH HHS / United States 5R01MH63706:02 / MH / NIMH NIH HHS / United States AG13196 / AG / NIA NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States RG08/01 / / British Heart Foundation / United Kingdom M01 RR16500 / RR / NCRR NIH HHS / United States U01 HL084756 / HL / NHLBI NIH HHS / United States R01 HL086694-05 / HL / NHLBI NIH HHS / United States MC_PC_U127527180 / / Medical Research Council / United Kingdom G8802774 / / Medical Research Council / United Kingdom R01 AG18728 / AG / NIA NIH HHS / United States G1000143 / / Medical Research Council / United Kingdom RG/08/013/25942 / / British Heart Foundation / United Kingdom G0902037 / / Medical Research Council / United Kingdom U01 GM074518-04 / GM / NIGMS NIH HHS / United States 1RL1MH083268-01 / MH / NIMH NIH HHS / United States R01 HL085251 / HL / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States R01HL060894 / HL / NHLBI NIH HHS / United States N01-HC-95165 / HC / NHLBI NIH HHS / United States U01HG004728 / HG / NHGRI NIH HHS / United States U01HG004399 / HG / NHGRI NIH HHS / United States 5U01CA086308 / CA / NCI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States MC_U137686857 / / Medical Research Council / United Kingdom ES10126 / ES / NIEHS NIH HHS / United States R01HL071252 / HL / NHLBI NIH HHS / United States U01 HL054471 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States FS05/125 / / British Heart Foundation / United Kingdom G0601966 / / Medical Research Council / United Kingdom G0500539 / / Medical Research Council / United Kingdom HL098283 / HL / NHLBI NIH HHS / United States TW05596 / TW / FIC NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States R01HL071205 / HL / NHLBI NIH HHS / United States U01HG004422 / HG / NHGRI NIH HHS / United States P30ES007033 / ES / NIEHS NIH HHS / United States DK072193 / DK / NIDDK NIH HHS / United States MC_U106179471 / / Medical Research Council / United Kingdom HG003054 / HG / NHGRI NIH HHS / United States HL084729 / HL / NHLBI NIH HHS / United States DK56350 / DK / NIDDK NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States RR20649 / RR / NCRR NIH HHS / United States R01 AG017644-09S1 / AG / NIA NIH HHS / United States / / Intramural NIH HHS / United States N01-HC-35129 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States 263-MA-410953 / / PHS HHS / United States N01-HD-1-3107 / HD / NICHD NIH HHS / United States MC_U123092720 / / Medical Research Council / United Kingdom HL085144 / HL / NHLBI NIH HHS / United States N01AG6210 / AG / NIA NIH HHS / United States HL36310 / HL / NHLBI NIH HHS / United States CZB/4/276 / / Chief Scientist Office / United Kingdom R01HL087641 / HL / NHLBI NIH HHS / United States U01 NS069208 / NS / NINDS NIH HHS / United States N01 HC-95159 / HC / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States 55005617 / / Howard Hughes Medical Institute / United States G0401527 / / Medical Research Council / United Kingdom HL45508 / HL / NHLBI NIH HHS / United States G0501942 / / Medical Research Council / United Kingdom MC_U123092723 / / Medical Research Council / United Kingdom N01-HC-95164 / HC / NHLBI NIH HHS / United States G0701863 / / Medical Research Council / United Kingdom SP/08/005/25115 / / British Heart Foundation / United Kingdom R37HL051021 / HL / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States U10 HL054512 / HL / NHLBI NIH HHS / United States 090532 / / Wellcome Trust / United Kingdom N01-HC-75150 / HC / NHLBI NIH HHS / United States U01HG004423 / HG / NHGRI NIH HHS / United States PG97027 / / British Heart Foundation / United Kingdom R01 HL086694-03 / HL / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01-HC-95160 / HC / NHLBI NIH HHS / United States N01 HC-15103 / HC / NHLBI NIH HHS / United States MOP-82810 / / Canadian Institutes of Health Research / Canada 080747/Z/06/Z / / Wellcome Trust / United Kingdom R01DK058845 / DK / NIDDK NIH HHS / United States U01DE018903 / DE / NIDCR NIH HHS / United States R01HL089650-02 / HL / NHLBI NIH HHS / United States MOP172605 / / Canadian Institutes of Health Research / Canada PG/02/128 / / British Heart Foundation / United Kingdom G0902313 / / Medical Research Council / United Kingdom U01HG004436 / HG / NHGRI NIH HHS / United States U01HG004729 / HG / NHGRI NIH HHS / United States R01HL056931 / HL / NHLBI NIH HHS / United States DK062370 / DK / NIDDK NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States U01 HL054466 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States U01 HL054466-11 / HL / NHLBI NIH HHS / United States N01-HC-45133 / HC / NHLBI NIH HHS / United States G0600331 / / Medical Research Council / United Kingdom R01DK066574 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01-HC-95161 / HC / NHLBI NIH HHS / United States N01AG62103 / AG / NIA NIH HHS / United States 5R01HL086694-03 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States CH/03/001 / / British Heart Foundation / United Kingdom 068545/Z/02 / / Wellcome Trust / United Kingdom HHSN268200782096C / / PHS HHS / United States 5R01HL087679-02 / HL / NHLBI NIH HHS / United States U10HL054512 / HL / NHLBI NIH HHS / United States HS06516 / HS / AHRQ HHS / United States HG005581 / HG / NHGRI NIH HHS / United States U01 HL072515-06 / HL / NHLBI NIH HHS / United States R01HL071259 / HL / NHLBI NIH HHS / United States U01DE01899 / DE / NIDCR NIH HHS / United States MOP77682 / / Canadian Institutes of Health Research / Canada HL087647 / HL / NHLBI NIH HHS / United States R01HL071251 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01-HC-95166 / HC / NHLBI NIH HHS / United States 2M01RR010284 / RR / NCRR NIH HHS / United States U01 HL054473 / HL / NHLBI NIH HHS / United States R03 TW007165 / TW / FIC NIH HHS / United States 1R01AG032098-01A / AG / NIA NIH HHS / United States R01HL071258 / HL / NHLBI NIH HHS / United States RG/08/014/24067 / / British Heart Foundation / United Kingdom 263 MD 9164 / MD / NIMHD NIH HHS / United States MC_U106188470 / / Medical Research Council / United Kingdom HL53353 / HL / NHLBI NIH HHS / United States 077016/Z/05/Z / / Wellcome Trust / United Kingdom R01HL071051 / HL / NHLBI NIH HHS / United States G0000934 / / Medical Research Council / United Kingdom RG/98002 / / British Heart Foundation / United Kingdom R01HL071250 / HL / NHLBI NIH HHS / United States R01 NS39987 / NS / NINDS NIH HHS / United States R01 DK078150 / DK / NIDDK NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States U01 DK062418 / DK / NIDDK NIH HHS / United States HL080025 / HL / NHLBI NIH HHS / United States R01 NS42733 / NS / NINDS NIH HHS / United States HHSN268200782096 / / PHS HHS / United States N01-HC-95167 / HC / NHLBI NIH HHS / United States 070191/Z/03/Z / / Wellcome Trust / United Kingdom R01HL086694 / HL / NHLBI NIH HHS / United States RG/07/008/23674 / / British Heart Foundation / United Kingdom |