Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • International Consortium for Blood Pressure Genome-Wide Association Studies, ; 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; 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, NC; 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; CARDIoGRAM consortium, ; CKDGen Consortium, ; KidneyGen Consortium, ; EchoGen consortium, ; CHARGE-HF consortium, ; 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, JH; Bis, JC; Kähönen, M; Viikari, J; Adair, LS; Lee, NR; Chen, M-H; Olden, M; Pattaro, C; Bolton, JAH; 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; Soler Artigas, M; 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; StanĨáková, A; Raffel, LJ; Yao, J; Kathiresan, S; O'Donnell, CJ; Schwartz, SM; Ikram, MA; 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, KR; Yajnik, CS; Hofman, A; Mattace-Raso, FUS; Oostra, BA; Demirkan, A; Isaacs, A; Rivadeneira, F; Lakatta, EG; Orru, 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, MVK; Denniff, M; Zukowska-Szczechowska, E; Wagenknecht, LE; Fowkes, FGR; 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, ES; 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; Järvelin, M-R; Psaty, BM; Abecasis, GR; Chakravarti, A; Elliott, P; van Duijn, CM; Newton-Cheh, C; Levy, D; Caulfield, MJ; Johnson, T

Published Date

  • September 11, 2011

Published In

Volume / Issue

  • 478 / 7367

Start / End Page

  • 103 - 109

PubMed ID

  • 21909115

Pubmed Central ID

  • 21909115

Electronic International Standard Serial Number (EISSN)

  • 1476-4687

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/nature10405

Language

  • eng