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

GB Ehret; PB Munroe; KM Rice; M Bochud; AD Johnson; DI Chasman; AV Smith; MD Tobin; Germaine Verwoert; SJ Hwang; V Pihur; P Vollenweider; PF O'Reilly; Najaf Amin; JL Bragg-Gresham; A Teumer; NL Glazer; L Launer; JH Zhao; Yuriy Aulchenko; S Heath; S Sober; A Parsa; JA Luan; M Arora; Abbas Dehghan; F Zhang; G Lucas; AA Hicks; AU Jackson; JF Peden; T Tanaka; SH Wild; I Rudan; W Igl; Y Milaneschi; AN Parker; C Fava; JC Chambers; ER Fox; M Kumari; MJ Go; P van der Harst; WHL Kao; M Sjogren; DG Vinay; M Alexander; Y Tabara; S Shaw-Hawkins; PH Whincup; YM Liu; G Shi; J Kuusisto; B Tayo; M Seielstad; X Sim; KDH Nguyen; T Lehtimaki; G Matullo; Fenny Wu; TR Gaunt; NC Onland-Moret; MN Cooper; CGP Platou; E Org; R Hardy; S Dahgam; J Palmen; V Vitart; PS Braund; T Kuznetsova; CSPM (Cuno) Uiterwaal; A Adeyemo; W Palmas; H Campbell; B Ludwig; M Tomaszewski; I Tzoulaki; ND Palmer; T Aspelund; M Garcia; YPC Chang; JR O'Connell; NI Steinle; DE (Diederick) Grobbee; DE Arking; SL Kardia; AC Morrison; D Hernandez; S Najjar; WL McArdle; D Hadley; MJ Brown; JM Connell; AD Hingorani; INM Day; DA Lawlor; JP Beilby; RW Lawrence; R Clarke; JC Hopewell; H Ongen; AW Dreisbach; YL Li; JH Young; JC Bis; M Kahonen; J Viikari; LS Adair; NR Lee; MH Chen; M Olden; C Pattaro; JAH Bolton; A Kottgen; S Bergmann; V Mooser; N Chaturvedi; TM Frayling; M Islam; TH Jafar; J Erdmann; SR Kulkarni; SR Bornstein; J Grassler; L Groop; BF Voight; J Kettunen; P Howard; A Taylor; S Guarrera; F Ricceri; V Emilsson; A Plump; IS Barroso; KT Khaw; AB Weder; SC Hunt; YV Sun; RN Bergman; FS Collins; LL Bonnycastle; LJ Scott; HM Stringham; L Peltonen; M Perola; E Vartiainen; SM Brand; JA Staessen; TJ Wang; PR Burton; MS Artigas; YB Dong; H Snieder; XL Wang; HD Zhu; KK Lohman; ME Rudock; SR Heckbert; NL Smith; KL Wiggins; A Doumatey; D Shriner; G Veldre; M Viigimaa; S Kinra; D Prabhakaran; V Tripathy; CD Langefeld; A Rosengren; DS Thelle; AM Corsi; A Singleton; T Forrester; G Hilton; CA McKenzie; T Salako; N Iwai; Y Kita; T Ogihara; T Ohkubo; Takayuki Okamura; H Ueshima; S Umemura; S Eyheramendy; T Meitinger; HE Wichmann; YS Cho; HL Kim; JY Lee; J Scott; JS Sehmi; WH Zhang; B Hedblad; P Nilsson; GD Smith; A Wong; N Narisu; A Stancakova; LJ Raffel; J (Jiefen) Yao; S Kathiresan; CJ O'Donnell; SM Schwartz; Arfan Ikram; WT Longstreth; TH Mosley; S Seshadri; NRG Shrine; LV Wain; MA Morken; AJ Swift; J Laitinen; I Prokopenko; P Zitting; JA Cooper; SE Humphries; J Danesh; A Rasheed; A Goel; A Hamsten; H Watkins; SJL Bakker; WH van Gilst; CS Janipalli; KR Mani; CS Yajnik; Bert Hofman; F.U.S. Mattace Raso; Ben Oostra; Ayse Demirkan; Aaron Isaacs; Fernando Rivadeneira; EG Lakatta; M Orru; A Scuteri; M Ala-Korpela; AJ Kangas; LP Lyytikainen; P Soininen; T Tukiainen; P Wurtz; RTH Ong; M Dorr; HK Kroemer; U Volker; H Volzke; P Galan; S Hercberg; M Lathrop; D Zelenika; P Deloukas; M Mangino; TD Spector; GJ Zhai; JF Meschia; MA Nalls; P Sharma; J Terzic; MVK Kumar; M Denniff; E Zukowska-Szczechowska; LE Wagenknecht; FGR Fowkes; FJ Charchar; PEH Schwarz; C Hayward; XQ Guo; C Rotimi; ML (Michiel) Bots; E (Eddy) Brand; NJ Samani; O Polasek; PJ Talmud; F Nyberg; D Kuh; M Laan; K Hveem; LJ Palmer; YT van der Schouw; JP Casas; KL Mohlke; P Vineis; O Raitakari; SK Ganesh; TY (Tien Yin) Wong; ES Tai; RS Cooper; M Laakso; DC Rao; TB Harris; RW Morris; AF Dominiczak; M Kivimaki; MG Marmot; T Miki; D Saleheen; GR Chandak; J Coresh; G Navis; V Salomaa; BG Han; XF Zhu; JS Kooner; O Melander; PM Ridker; S Bandinelli; UB Gyllensten; AF Wright; JF Wilson; L Ferrucci; M Farrall; J Tuomilehto; PP Pramstaller; R Elosua; N Soranzo; E.J.G. Sijbrands; D Altshuler; RJF Loos; AR Shuldiner; C Gieger; P Meneton; André Uitterlinden; NJ Wareham; V Gudnason; JI Rotter; R Rettig; M Uda; DP Strachan; JCM Witteman; AL Hartikainen; JS Beckmann; E Boerwinkle; RS Vasan; M Boehnke; MG Larson; MR Jarvelin; BM Psaty; GR Abecasis; A Chakravarti; P Elliott; Cornelia Duijn; C Newton-Cheh; D Levy; MJ Caulfield; T Johnson

doi:10.1038/nature10405

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

GB Ehret
, PB Munroe
, KM Rice
, M Bochud
, AD Johnson
, DI Chasman
, AV Smith
, MD Tobin
, Germaine Verwoert
, SJ Hwang
, V Pihur
, P Vollenweider
, PF O'Reilly
, Najaf Amin
, JL Bragg-Gresham
, A Teumer
, NL Glazer
, L Launer
, JH Zhao
, Yuriy Aulchenko

S Heath, S Sober, A Parsa, JA Luan, M Arora, Abbas Dehghan, F Zhang, G Lucas, AA Hicks, AU Jackson, JF Peden, T Tanaka, SH Wild, I Rudan, W Igl, Y Milaneschi, AN Parker, C Fava, JC Chambers, ER Fox, M Kumari, MJ Go, P van der Harst, WHL Kao, M Sjogren, DG Vinay, M Alexander, Y Tabara, S Shaw-Hawkins, PH Whincup, YM Liu, G Shi, J Kuusisto, B Tayo, M Seielstad, X Sim, KDH Nguyen, T Lehtimaki, G Matullo, Fenny Wu, TR Gaunt, NC Onland-Moret, MN Cooper, CGP Platou, E Org, R Hardy, S Dahgam, J Palmen, V Vitart, PS Braund, T Kuznetsova, CSPM (Cuno) Uiterwaal, A Adeyemo, W Palmas, H Campbell, B Ludwig, M Tomaszewski, I Tzoulaki, ND Palmer, T Aspelund, M Garcia, YPC Chang, JR O'Connell, NI Steinle, DE (Diederick) Grobbee, DE Arking, SL Kardia, AC Morrison, D Hernandez, S Najjar, WL McArdle, D Hadley, MJ Brown, JM Connell, AD Hingorani, INM Day, DA Lawlor, JP Beilby, RW Lawrence, R Clarke, JC Hopewell, H Ongen, AW Dreisbach, YL Li, JH Young, JC Bis, M Kahonen, J Viikari, LS Adair, NR Lee, MH Chen, M Olden, C Pattaro, JAH Bolton, A Kottgen, S Bergmann, V Mooser, N Chaturvedi, TM Frayling, M Islam, TH Jafar, J Erdmann, SR Kulkarni, SR Bornstein, J Grassler, L Groop, BF Voight, J Kettunen, P Howard, A Taylor, S Guarrera, F Ricceri, V Emilsson, A Plump, IS Barroso, KT Khaw, AB Weder, SC Hunt, YV Sun, RN Bergman, FS Collins, LL Bonnycastle, LJ Scott, HM Stringham, L Peltonen, M Perola, E Vartiainen, SM Brand, JA Staessen, TJ Wang, PR Burton, MS Artigas, YB Dong, H Snieder, XL Wang, HD Zhu, KK Lohman, ME Rudock, SR Heckbert, NL Smith, KL Wiggins, A Doumatey, D Shriner, G Veldre, M Viigimaa, S Kinra, D Prabhakaran, V Tripathy, CD Langefeld, A Rosengren, DS Thelle, AM Corsi, A Singleton, T Forrester, G Hilton, CA McKenzie, T Salako, N Iwai, Y Kita, T Ogihara, T Ohkubo, Takayuki Okamura, H Ueshima, S Umemura, S Eyheramendy, T Meitinger, HE Wichmann, YS Cho, HL Kim, JY Lee, J Scott, JS Sehmi, WH Zhang, B Hedblad, P Nilsson, GD Smith, A Wong, N Narisu, A Stancakova, LJ Raffel, J (Jiefen) Yao, S Kathiresan, CJ O'Donnell, SM Schwartz, Arfan Ikram, WT Longstreth, TH Mosley, S Seshadri, NRG Shrine, LV Wain, MA Morken, AJ Swift, J Laitinen, I Prokopenko, P Zitting, JA Cooper, SE Humphries, J Danesh, A Rasheed, A Goel, A Hamsten, H Watkins, SJL Bakker, WH van Gilst, CS Janipalli, KR Mani, CS Yajnik, Bert Hofman, F.U.S. Mattace Raso, Ben Oostra, Ayse Demirkan, Aaron Isaacs, Fernando Rivadeneira, EG Lakatta, M Orru, A Scuteri, M Ala-Korpela, AJ Kangas, LP Lyytikainen, P Soininen, T Tukiainen, P Wurtz, RTH Ong, M Dorr, HK Kroemer, U Volker, H Volzke, P Galan, S Hercberg, M Lathrop, D Zelenika, P Deloukas, M Mangino, TD Spector, GJ Zhai, JF Meschia, MA Nalls, P Sharma, J Terzic, MVK Kumar, M Denniff, E Zukowska-Szczechowska, LE Wagenknecht, FGR Fowkes, FJ Charchar, PEH Schwarz, C Hayward, XQ Guo, C Rotimi, ML (Michiel) Bots, E (Eddy) Brand, NJ Samani, O Polasek, PJ Talmud, F Nyberg, D Kuh, M Laan, K Hveem, LJ Palmer, YT van der Schouw, JP Casas, KL Mohlke, P Vineis, O Raitakari, SK Ganesh, TY (Tien Yin) Wong, ES Tai, RS Cooper, M Laakso, DC Rao, TB Harris, RW Morris, AF Dominiczak, M Kivimaki, MG Marmot, T Miki, D Saleheen, GR Chandak, J Coresh, G Navis, V Salomaa, BG Han, XF Zhu, JS Kooner, O Melander, PM Ridker, S Bandinelli, UB Gyllensten, AF Wright, JF Wilson, L Ferrucci, M Farrall, J Tuomilehto, PP Pramstaller, R Elosua, N Soranzo, E.J.G. Sijbrands, D Altshuler, RJF Loos, AR Shuldiner, C Gieger, P Meneton, André Uitterlinden, NJ Wareham, V Gudnason, JI Rotter, R Rettig, M Uda, DP Strachan, JCM Witteman, AL Hartikainen, JS Beckmann, E Boerwinkle, RS Vasan, M Boehnke, MG Larson, MR Jarvelin, BM Psaty, GR Abecasis, A Chakravarti, P Elliott, Cornelia Duijn, C Newton-Cheh, D Levy, MJ Caulfield, T Johnson

External organisation

Research output: Contribution to journal › Article › Academic › peer-review

1795 Citations (Scopus)

Abstract

Blood pressure is a heritable trait(1) 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)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). 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.

Original language	Undefined/Unknown
Pages (from-to)	103-109
Number of pages	7
Journal	Nature
Volume	478
Issue number	7367
DOIs	https://doi.org/10.1038/nature10405
Publication status	Published - 2011

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research programs

EMC COEUR-09
EMC MGC-02-96-01
EMC MM-01-25-01
EMC MM-01-39-09-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC NIHES-03-77-02
EMC OR-01-39-08

Access to Document

10.1038/nature10405

http://hdl.handle.net/1765/33262

Cite this

Ehret, GB., Munroe, PB., Rice, KM., Bochud, M., Johnson, AD., Chasman, DI., Smith, AV., Tobin, MD., Verwoert, G., Hwang, SJ., Pihur, V., Vollenweider, P., O'Reilly, PF., Amin, N., Bragg-Gresham, JL., Teumer, A., Glazer, NL., Launer, L., Zhao, JH., ... Johnson, T. (2011). Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature, 478(7367), 103-109. https://doi.org/10.1038/nature10405

@article{f57232da42c642e6ada978cfb79094d0,

title = "Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk",

abstract = "Blood pressure is a heritable trait(1) 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)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). 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.",

author = "GB Ehret and PB Munroe and KM Rice and M Bochud and AD Johnson and DI Chasman and AV Smith and MD Tobin and Germaine Verwoert and SJ Hwang and V Pihur and P Vollenweider and PF O'Reilly and Najaf Amin and JL Bragg-Gresham and A Teumer and NL Glazer and L Launer and JH Zhao and Yuriy Aulchenko and S Heath and S Sober and A Parsa and JA Luan and M Arora and Abbas Dehghan and F Zhang and G Lucas and AA Hicks and AU Jackson and JF Peden and T Tanaka and SH Wild and I Rudan and W Igl and Y Milaneschi and AN Parker and C Fava and JC Chambers and ER Fox and M Kumari and MJ Go and \{van der Harst\}, P and WHL Kao and M Sjogren and DG Vinay and M Alexander and Y Tabara and S Shaw-Hawkins and PH Whincup and YM Liu and G Shi and J Kuusisto and B Tayo and M Seielstad and X Sim and KDH Nguyen and T Lehtimaki and G Matullo and Fenny Wu and TR Gaunt and NC Onland-Moret and MN Cooper and CGP Platou and E Org and R Hardy and S Dahgam and J Palmen and V Vitart and PS Braund and T Kuznetsova and Uiterwaal, \{CSPM (Cuno)\} and A Adeyemo and W Palmas and H Campbell and B Ludwig and M Tomaszewski and I Tzoulaki and ND Palmer and T Aspelund and M Garcia and YPC Chang and JR O'Connell and NI Steinle and Grobbee, \{DE (Diederick)\} and DE Arking and SL Kardia and AC Morrison and D Hernandez and S Najjar and WL McArdle and D Hadley and MJ Brown and JM Connell and AD Hingorani and INM Day and DA Lawlor and JP Beilby and RW Lawrence and R Clarke and JC Hopewell and H Ongen and AW Dreisbach and YL Li and JH Young and JC Bis and M Kahonen and J Viikari and LS Adair and NR Lee and MH Chen and M Olden and C Pattaro and JAH Bolton and A Kottgen and S Bergmann and V Mooser and N Chaturvedi and TM Frayling and M Islam and TH Jafar and J Erdmann and SR Kulkarni and SR Bornstein and J Grassler and L Groop and BF Voight and J Kettunen and P Howard and A Taylor and S Guarrera and F Ricceri and V Emilsson and A Plump and IS Barroso and KT Khaw and AB Weder and SC Hunt and YV Sun and RN Bergman and FS Collins and LL Bonnycastle and LJ Scott and HM Stringham and L Peltonen and M Perola and E Vartiainen and SM Brand and JA Staessen and TJ Wang and PR Burton and MS Artigas and YB Dong and H Snieder and XL Wang and HD Zhu and KK Lohman and ME Rudock and SR Heckbert and NL Smith and KL Wiggins and A Doumatey and D Shriner and G Veldre and M Viigimaa and S Kinra and D Prabhakaran and V Tripathy and CD Langefeld and A Rosengren and DS Thelle and AM Corsi and A Singleton and T Forrester and G Hilton and CA McKenzie and T Salako and N Iwai and Y Kita and T Ogihara and T Ohkubo and Takayuki Okamura and H Ueshima and S Umemura and S Eyheramendy and T Meitinger and HE Wichmann and YS Cho and HL Kim and JY Lee and J Scott and JS Sehmi and WH Zhang and B Hedblad and P Nilsson and GD Smith and A Wong and N Narisu and A Stancakova and LJ Raffel and Yao, \{J (Jiefen)\} and S Kathiresan and CJ O'Donnell and SM Schwartz and Arfan Ikram and WT Longstreth and TH Mosley and S Seshadri and NRG Shrine and LV Wain and MA Morken and AJ Swift and J Laitinen and I Prokopenko and P Zitting and JA Cooper and SE Humphries and J Danesh and A Rasheed and A Goel and A Hamsten and H Watkins and SJL Bakker and \{van Gilst\}, WH and CS Janipalli and KR Mani and CS Yajnik and Bert Hofman and \{Mattace Raso\}, F.U.S. and Ben Oostra and Ayse Demirkan and Aaron Isaacs and Fernando Rivadeneira and EG Lakatta and M Orru and A Scuteri and M Ala-Korpela and AJ Kangas and LP Lyytikainen and P Soininen and T Tukiainen and P Wurtz and RTH Ong and M Dorr and HK Kroemer and U Volker and H Volzke and P Galan and S Hercberg and M Lathrop and D Zelenika and P Deloukas and M Mangino and TD Spector and GJ Zhai and JF Meschia and MA Nalls and P Sharma and J Terzic and MVK Kumar and M Denniff and E Zukowska-Szczechowska and LE Wagenknecht and FGR Fowkes and FJ Charchar and PEH Schwarz and C Hayward and XQ Guo and C Rotimi and Bots, \{ML (Michiel)\} and Brand, \{E (Eddy)\} and NJ Samani and O Polasek and PJ Talmud and F Nyberg and D Kuh and M Laan and K Hveem and LJ Palmer and \{van der Schouw\}, YT and JP Casas and KL Mohlke and P Vineis and O Raitakari and SK Ganesh and Wong, \{TY (Tien Yin)\} and ES Tai and RS Cooper and M Laakso and DC Rao and TB Harris and RW Morris and AF Dominiczak and M Kivimaki and MG Marmot and T Miki and D Saleheen and GR Chandak and J Coresh and G Navis and V Salomaa and BG Han and XF Zhu and JS Kooner and O Melander and PM Ridker and S Bandinelli and UB Gyllensten and AF Wright and JF Wilson and L Ferrucci and M Farrall and J Tuomilehto and PP Pramstaller and R Elosua and N Soranzo and E.J.G. Sijbrands and D Altshuler and RJF Loos and AR Shuldiner and C Gieger and P Meneton and Andr{\'e} Uitterlinden and NJ Wareham and V Gudnason and JI Rotter and R Rettig and M Uda and DP Strachan and JCM Witteman and AL Hartikainen and JS Beckmann and E Boerwinkle and RS Vasan and M Boehnke and MG Larson and MR Jarvelin and BM Psaty and GR Abecasis and A Chakravarti and P Elliott and Cornelia Duijn and C Newton-Cheh and D Levy and MJ Caulfield and T Johnson",

year = "2011",

doi = "10.1038/nature10405",

language = "Undefined/Unknown",

volume = "478",

pages = "103--109",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7367",

}

Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Johnson, AD, Chasman, DI, Smith, AV, Tobin, MD, Verwoert, G, Hwang, SJ, Pihur, V, Vollenweider, P, O'Reilly, PF, Amin, N, Bragg-Gresham, JL, Teumer, A, Glazer, NL, Launer, L, Zhao, JH, Aulchenko, Y, Heath, S, Sober, S, Parsa, A, Luan, JA, Arora, M, 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, Sjogren, M, Vinay, DG, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, PH, Liu, YM, Shi, G, Kuusisto, J, Tayo, B, Seielstad, M, Sim, X, Nguyen, KDH, Lehtimaki, T, Matullo, G, Wu, F, 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, Aspelund, T, Garcia, M, Chang, YPC, 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, YL, Young, JH, Bis, JC, Kahonen, M, Viikari, J, Adair, LS, Lee, NR, Chen, MH, Olden, M, Pattaro, C, Bolton, JAH, Kottgen, A, Bergmann, S, Mooser, V, Chaturvedi, N, Frayling, TM, Islam, M, Jafar, TH, Erdmann, J, Kulkarni, SR, Bornstein, SR, Grassler, J, Groop, L, Voight, BF, Kettunen, J, Howard, P, Taylor, A, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Barroso, IS, Khaw, KT, Weder, AB, Hunt, SC, Sun, YV, Bergman, RN, Collins, FS, Bonnycastle, LL, Scott, LJ, Stringham, HM, Peltonen, L, Perola, M, Vartiainen, E, Brand, SM, Staessen, JA, Wang, TJ, Burton, PR, Artigas, MS, Dong, YB, Snieder, H, Wang, XL, Zhu, HD, 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, HE, Cho, YS, Kim, HL, Lee, JY, Scott, J, Sehmi, JS, Zhang, WH, Hedblad, B, Nilsson, P, Smith, GD, Wong, A, Narisu, N, Stancakova, A, Raffel, LJ, Yao, J, Kathiresan, S, O'Donnell, CJ, Schwartz, SM, Ikram, A, 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, B, Mattace Raso, FUS, Oostra, B, Demirkan, A, Isaacs, A, Rivadeneira, F, Lakatta, EG, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, AJ, Lyytikainen, LP, Soininen, P, Tukiainen, T, Wurtz, P, Ong, RTH, Dorr, M, Kroemer, HK, Volker, U, Volzke, H, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Deloukas, P, Mangino, M, Spector, TD, Zhai, GJ, 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, XQ, 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, BG, Zhu, XF, 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, A, Wareham, NJ, Gudnason, V, Rotter, JI, Rettig, R, Uda, M, Strachan, DP, Witteman, JCM, Hartikainen, AL, Beckmann, JS, Boerwinkle, E, Vasan, RS, Boehnke, M, Larson, MG, Jarvelin, MR, Psaty, BM, Abecasis, GR, Chakravarti, A, Elliott, P, Duijn, C, Newton-Cheh, C, Levy, D, Caulfield, MJ & Johnson, T 2011, 'Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk', Nature, vol. 478, no. 7367, pp. 103-109. https://doi.org/10.1038/nature10405

TY - JOUR

T1 - Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk

AU - Ehret, GB

AU - Munroe, PB

AU - Rice, KM

AU - Bochud, M

AU - Johnson, AD

AU - Chasman, DI

AU - Smith, AV

AU - Tobin, MD

AU - Verwoert, Germaine

AU - Hwang, SJ

AU - Pihur, V

AU - Vollenweider, P

AU - O'Reilly, PF

AU - Amin, Najaf

AU - Bragg-Gresham, JL

AU - Teumer, A

AU - Glazer, NL

AU - Launer, L

AU - Zhao, JH

AU - Aulchenko, Yuriy

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PY - 2011

Y1 - 2011

N2 - Blood pressure is a heritable trait(1) 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)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). 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.

AB - Blood pressure is a heritable trait(1) 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)(2). Even small increments in blood pressure are associated with an increased risk of cardiovascular events(3). 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.

U2 - 10.1038/nature10405

DO - 10.1038/nature10405

M3 - Article

C2 - 21909115

SN - 0028-0836

VL - 478

SP - 103

EP - 109

JO - Nature

JF - Nature

IS - 7367

ER -