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

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
Sober, 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
Sjogren, M
Vinay, DG
Alexander, M
Tabara, Y
Shaw-Hawkins, S
Whincup, PH
Liu, Y
Shi, G
Kuusisto, J
Tayo, B
Seielstad, M
Sim, X
Khanh-Dung, HN
Lehtimaki, 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
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
Kahonen, M
Viikari, J
Adair, LS
Lee, NR
Chen, M-H
Olden, M
Pattaro, C
Bolton, JAH
Koettgen, A
Bergmann, S
Mooser, V
Chaturvedi, N
Frayling, TM
Islam, M
Jafar, TH
Erdmann, J
Kulkarni, SR
Bornstein, SR
Graessler, J
Groop, L
Voight, BF
Kettunen, J
Howard, P
Taylor, A
Guarrera, S
Ricceri, F
Emilsson, V
Plump, A
Barroso, IS
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, MS
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
Stancakova, 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
Lyytikainen, L-P
Soininen, P
Tukiainen, T
Wurtz, P
Ong, RT-H
Doerr, M
Kroemer, HK
Voelker, U
Voelzke, 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
Jarvelin, M-R
Psaty, BM
Abecasis, GR
Chakravarti, A
Elliott, P
van Duijn, CM
Newton-Cheh, C
Levy, D
Caulfield, MJ
Johnson, T
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
Sober, 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
Sjogren, M
Vinay, DG
Alexander, M
Tabara, Y
Shaw-Hawkins, S
Whincup, PH
Liu, Y
Shi, G
Kuusisto, J
Tayo, B
Seielstad, M
Sim, X
Khanh-Dung, HN
Lehtimaki, 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
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
Kahonen, M
Viikari, J
Adair, LS
Lee, NR
Chen, M-H
Olden, M
Pattaro, C
Bolton, JAH
Koettgen, A
Bergmann, S
Mooser, V
Chaturvedi, N
Frayling, TM
Islam, M
Jafar, TH
Erdmann, J
Kulkarni, SR
Bornstein, SR
Graessler, J
Groop, L
Voight, BF
Kettunen, J
Howard, P
Taylor, A
Guarrera, S
Ricceri, F
Emilsson, V
Plump, A
Barroso, IS
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, MS
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
Stancakova, 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
Lyytikainen, L-P
Soininen, P
Tukiainen, T
Wurtz, P
Ong, RT-H
Doerr, M
Kroemer, HK
Voelker, U
Voelzke, 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
Jarvelin, M-R
Psaty, BM
Abecasis, GR
Chakravarti, A
Elliott, P
van Duijn, CM
Newton-Cheh, C
Levy, D
Caulfield, MJ
Johnson, T
Publication Year :
2011

Abstract

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.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1315687538
Document Type :
Electronic Resource