Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Warren, H.; Evangelou, E.; Cabrera, C.; Gao, H.; Ren, M.; Mifsud, B.; Ntalla, I.; Surendran, P.; Liu, C.; Cook, J.; Kraja, A.; Drenos, F.; Loh, M.; Verweij, N.; Marten, J.; Karaman, I.; Mps, L.; O'Reilly, P.; Knight, J.; Snieder, H.; Kato, N.; J, H.; Tai, E.; Said, M.; Porteous, D.; Alver, M.; Poulter, N.; Farrall, M.; Gansevoort, R.; Padmanabhan, S.; Magi, R.; Stanton, A.; Connell, J.; Sjl, B.; Metspalu, A.; Shields, D.; Thom, S.; Brown, M.; Sever, P.; Esko, T.; Hayward, C.; van der Harst, P.; Saleheen, D.; Chowdhury, R.; Chambers, J.; Chasman, D.; Chakravarti, A.; Newton-Cheh, C.; Lindgren, C.; Levy, D.; Kooner, J.; Keavney, B.; Tomaszewski, M.; Samani, N.; Jmm, H.; Tobin, M.; Munroe, P.; Ehret, G.; Wain, L.; Barnes, M.; Tzoulaki, J.; Caulfield, M.; Elliott, P.; Wain, L.; Vaez, A.; Jansen, R.; Joehanes, R.; van der Most PJ,; Erzurumluoglu, A.; O'Reilly, P.; Cabrera, C.; Warren, H.; Rose, L.; Verwoert, G.; Hottenga, J.; Strawbridge, R.; Esko, T.; Arking, D.; Hwang, S.; Guo, X.; Kutalik, Z.; Trompet, S.; Shrine, N.; Teumer, A.; Ried, J.; Bis, J.; Smith, A.; Amin, N.; Nolte, I.; Lyytikainen, L.; Mahajan, A.; Wareham, N.; Hofer, E.; Joshi, P.; Kristiansson, K.; Traglia, M.; Havulinna, A.; Goel, A.; Nalls, M.; Sober, S.; Vuckovic, D.; Luan, J.; Del Greco, F.; Ayers, K.; Marrugat, J.; Ruggiero, D.; Lopez, L.; Niiranen, T.; Enroth, S.; Jackson, A.; Nelson, C.; Huffman, J.; Zhang, W.; Marten, J.; Gandin, I.; Harris, S.; Zemonik, T.; Yc, L.; Evangelou, E.; Shah, N.; de Borst MH,; Mangino, M.; Prins, B.; Campbell, A.; Li-Gao, R.; Chauhan, G.; Oldmeadow, C.; Abecasis, G.; Abedi, M.; Barbieri, C.; Barnes, M.; Batini, C.; Blake, T.; Boehnke, M.; Bottinger, E.; Braund, P.; Brown, M.; Brumat, M.; Campbell, H.; Chambers, J.; Cocca, M.; Collins, F.; Connell, J.; Cordell, H.; Damman, J.; Davies, G.; de Geus EJ,; de Mutsert, R.; Deelen, J.; Demirkale, Y.; Asf, D.; Dorr, M.; Farrall, M.; Ferreira, T.; Franberg, M.; Gao, H.; Giedraitis, V.; Gieger, C.; Giulianini, F.; Gow, A.; Hamsten, A.; Harris, T.; Hofman, A.; Holliday, E.; Jarvelin, M.; Johansson, A.; Johnson, A.; Jousilahti, P.; Jula, A.; Kahonen, M.; Kathiresan, S.; Khaw, K.; Kolcic, I.; Koskinen, S.; Langenberg, C.; Larson, M.; Launer, L.; Lehne, B.; Dcm, L.; Lin, L.; Lind, L.; Mach, F.; Mamasoula, C.; Menni, C.; Mifsud, B.; Milaneschi, Y.; Morgan, A.; Morris, A.; Morrison, A.; Munson, P.; Nandakumar, P.; Nguyen, Q.; Nutile, T.; Oldehinkel, A.; Oostra, B.; Org, E.; Padmanabhan, S.; Palotie, A.; Pare, G.; Pattie, A.; Bwjh, P.; Poulter, N.; Pramstaller, P.; Raitakari, O.; Ren, M.; Rice, K.; Ridker, P.; Riese, H.; Ripatti, S.; Robino, A.; Rotter, J.; Rudan, I.; Saba, Y.; Saint Pierre, A.; Sala, C.; Sarin, A.; Schmidt, R.; Scott, R.; Seelen, M.; Shields, D.; Siscovick, D.; Sorice, R.; Stanton, A.; Stott, D.; Sundstrom, J.; Swertz, M.; Taylor, K.; Thom, S.; Tzoulaki, I.; Tzourio, C.; Uitterlinden, A.; Volker, U.; Vollenweider, P.; Wild, S.; Willemsen, G.; Wright, A.; Yao, J.; Theriault, S.; Conen, D.; John, A.; Sever, P.; Debette, S.; Mook-Kanamori, D.; Zeggini, E.; Spector, T.; van der Harst, P.; Cna, P.; Vergnaud, A.; Rjf, L.; Polasek, O.; Starr, J.; Girotto, G.; Hayward, C.; Kooner, J.; Lindgren, C.; Vitart, V.; Samani, N.; Tuomilehto, J.; Gyllensten, U.; Knekt, P.; Deary, I.; Ciullo, M.; Elosua, R.; Keavney, B.; Hicks, A.; Scott, R.; Gasparini, P.; Laan, M.; Liu, Y.; Watkins, H.; Hartman, C.; Salomaa, V.; Toniolo, D.; Perola, M.; Wilson, J.; Schmidt, H.; Zhao, J.; Lehtimaki, T.; van Duijn CM,; Gudnason, V.; Psaty, B.; Peters, A.; Rettig, R.; James, A.; Jukema, J.; Strachan, D.; Palmas, W.; Metspalu, A.; Ingelsson, E.; Boomsma, D.; Franco, O.; Bochud, M.; Newton-Cheh, C.; Munroe, P.; Elliott, P.; Chasman, D.; Chakravarti, A.; Knight, J.; Morris, A.; Levy, D.; Tobin, M.; Snieder, H.; Caulfield, M.; Ehret, G.

doi:10.1038/ng.3768

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk / H. Warren, E. Evangelou, C. Cabrera, H. Gao, M. Ren, B. Mifsud, I. Ntalla, P. Surendran, C. Liu, J. Cook, A. Kraja, F. Drenos, M. Loh, N. Verweij, J. Marten, I. Karaman, M. Lepe, P. O'Reilly, J. Knight, H. Snieder, N. Kato, J. He, E. Tai, M. Said, D. Porteous, M. Alver, N. Poulter, M. Farrall, R. Gansevoort, S. Padmanabhan, R. Magi, A. Stanton, J. Connell, S. Bakker, A. Metspalu, D. Shields, S. Thom, M. Brown, P. Sever, T. Esko, C. Hayward, P. van der Harst, D. Saleheen, R. Chowdhury, J. Chambers, D. Chasman, A. Chakravarti, C. Newton-Cheh, C. Lindgren, D. Levy, J. Kooner, B. Keavney, M. Tomaszewski, N. Samani, J. Howson, M. Tobin, P. Munroe, G. Ehret, L. Wain, M. Barnes, J. Tzoulaki, M. Caulfield, P. Elliott, L. Wain, A. Vaez, R. Jansen, R. Joehanes, P. van der Most, A. Erzurumluoglu, P. O'Reilly, C. Cabrera, H. Warren, L. Rose, G. Verwoert, J. Hottenga, R. Strawbridge, T. Esko, D. Arking, S. Hwang, X. Guo, Z. Kutalik, S. Trompet, N. Shrine, A. Teumer, J. Ried, J. Bis, A. Smith, N. Amin, I. Nolte, L. Lyytikainen, A. Mahajan, N. Wareham, E. Hofer, P. Joshi, K. Kristiansson, M. Traglia, A. Havulinna, A. Goel, M. Nalls, S. Sober, D. Vuckovic, J. Luan, F. Del Greco, K. Ayers, J. Marrugat, D. Ruggiero, L. Lopez, T. Niiranen, S. Enroth, A. Jackson, C. Nelson, J. Huffman, W. Zhang, J. Marten, I. Gandin, S. Harris, T. Zemonik, Y. Lu, E. Evangelou, N. Shah, M. de Borst, M. Mangino, B. Prins, A. Campbell, R. Li-Gao, G. Chauhan, C. Oldmeadow, G. Abecasis, M. Abedi, C. Barbieri, M. Barnes, C. Batini, T. Blake, M. Boehnke, E. Bottinger, P. Braund, M. Brown, M. Brumat, H. Campbell, J. Chambers, M. Cocca, F. Collins, J. Connell, H. Cordell, J. Damman, G. Davies, E. de Geus, R. de Mutsert, J. Deelen, Y. Demirkale, A. Doney, M. Dorr, M. Farrall, T. Ferreira, M. Franberg, H. Gao, V. Giedraitis, C. Gieger, F. Giulianini, A. Gow, A. Hamsten, T. Harris, A. Hofman, E. Holliday, M. Jarvelin, A. Johansson, A. Johnson, P. Jousilahti, A. Jula, M. Kahonen, S. Kathiresan, K. Khaw, I. Kolcic, S. Koskinen, C. Langenberg, M. Larson, L. Launer, B. Lehne, D. Liewald, L. Lin, L. Lind, F. Mach, C. Mamasoula, C. Menni, B. Mifsud, Y. Milaneschi, A. Morgan, A. Morris, A. Morrison, P. Munson, P. Nandakumar, Q. Nguyen, T. Nutile, A. Oldehinkel, B. Oostra, E. Org, S. Padmanabhan, A. Palotie, G. Pare, A. Pattie, B. Penninx, N. Poulter, P. Pramstaller, O. Raitakari, M. Ren, K. Rice, P. Ridker, H. Riese, S. Ripatti, A. Robino, J. Rotter, I. Rudan, Y. Saba, A. Saint Pierre, C. Sala, A. Sarin, R. Schmidt, R. Scott, M. Seelen, D. Shields, D. Siscovick, R. Sorice, A. Stanton, D. Stott, J. Sundstrom, M. Swertz, K. Taylor, S. Thom, I. Tzoulaki, C. Tzourio, A. Uitterlinden, U. Volker, P. Vollenweider, S. Wild, G. Willemsen, A. Wright, J. Yao, S. Theriault, D. Conen, A. John, P. Sever, S. Debette, D. Mook-Kanamori, E. Zeggini, T. Spector, P. van der Harst, C. Palmer, A. Vergnaud, R. Loos, O. Polasek, J. Starr, G. Girotto, C. Hayward, J. Kooner, C. Lindgren, V. Vitart, N. Samani, J. Tuomilehto, U. Gyllensten, P. Knekt, I. Deary, M. Ciullo, R. Elosua, B. Keavney, A. Hicks, R. Scott, P. Gasparini, M. Laan, Y. Liu, H. Watkins, C. Hartman, V. Salomaa, D. Toniolo, M. Perola, J. Wilson, H. Schmidt, J. Zhao, T. Lehtimaki, C. van Duijn, V. Gudnason, B. Psaty, A. Peters, R. Rettig, A. James, J. Jukema, D. Strachan, W. Palmas, A. Metspalu, E. Ingelsson, D. Boomsma, O. Franco, M. Bochud, C. Newton-Cheh, P. Munroe, P. Elliott, D. Chasman, A. Chakravarti, J. Knight, A. Morris, D. Levy, M. Tobin, H. Snieder, M. Caulfield, G. Ehret. - In: NATURE GENETICS. - ISSN 1061-4036. - 49:3(2017), pp. 403-415. [10.1038/ng.3768]

Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk

Warren HR;Evangelou E;Cabrera CP;Gao H;Ren MX;Mifsud B;Ntalla I;Surendran P;Liu CY;Cook JP;Kraja AT;Drenos F;Loh M;Verweij N;Marten J;Karaman I;Lepe MPS;O'Reilly PF;Knight J;Snieder H;Kato N;He J;Tai ES;Said MA;Porteous D;Alver M;Poulter N;Farrall M;Gansevoort RT;Padmanabhan S;Magi R;Stanton A;Connell J;Bakker SJL;Metspalu A;Shields DC;Thom S;Brown M;Sever P;Esko T;Hayward C;van der Harst P;Saleheen D;Chowdhury R;Chambers JC;Chasman DI;Chakravarti A;Newton-Cheh C;Lindgren CM;Levy D;Kooner JS;Keavney B;Tomaszewski M;Samani NJ;Howson JMM;Tobin MD;Munroe PB;Ehret GB;Wain LV;Barnes MR;Tzoulaki J;Caulfield MJ;Elliott P;Wain LV;Vaez A;Jansen R;Joehanes R;van der Most PJ;Erzurumluoglu AM;O'Reilly P;Cabrera CP;Warren HR;Rose LM;Verwoert GC;Hottenga JJ;Strawbridge RJ;Esko T;Arking DE;Hwang SJ;Guo XQ;Kutalik Z;Trompet S;Shrine N;Teumer A;Ried JS;Bis JC;Smith AV;Amin N;Nolte IM;Lyytikainen LP;Mahajan A;Wareham NJ;Hofer E;Joshi PK;Kristiansson K;Traglia M;Havulinna AS;Goel A;Nalls MA;Sober S;Vuckovic D;Luan JA;Del Greco F;Ayers KL;Marrugat J;Ruggiero D;Lopez LM;Niiranen T;Enroth S;Jackson AU;Nelson CP;Huffman JE;Zhang WH;Marten J;Gandin I;Harris SE;Zemonik T;Lu YC;Evangelou E;Shah N;de Borst MH;Mangino M;Prins BP;Campbell A;Li-Gao RF;Chauhan G;Oldmeadow C;Abecasis G;Abedi M;Barbieri CM;Barnes MR;Batini C;Blake T;Boehnke M;Bottinger EP;Braund PS;Brown M;Brumat M;Campbell H;Chambers JC;Cocca M;Collins F;Connell J;Cordell HJ;Damman JJ;Davies G;de Geus EJ;de Mutsert R;Deelen J;Demirkale Y;Doney ASF;Dorr M;Farrall M;Ferreira T;Franberg M;Gao H;Giedraitis V;Gieger C;Giulianini F;Gow AJ;Hamsten A;Harris TB;Hofman A;Holliday EG;Jarvelin MR;Johansson A;Johnson AD;Jousilahti P;Jula A;Kahonen M;Kathiresan S;Khaw KT;Kolcic I;Koskinen S;Langenberg C;Larson M;Launer LJ;Lehne B;Liewald DCM;Lin L;Lind L;Mach F;Mamasoula C;C. Menni;Mifsud B;Milaneschi Y;Morgan A;Morris AD;Morrison AC;Munson PJ;Nandakumar P;Nguyen QT;Nutile T;Oldehinkel AJ;Oostra BA;Org E;Padmanabhan S;Palotie A;Pare G;Pattie A;Penninx BWJH;Poulter N;Pramstaller PP;Raitakari OT;Ren MX;Rice K;Ridker PM;Riese H;Ripatti S;Robino A;Rotter JI;Rudan I;Saba Y;Saint Pierre A;Sala CF;Sarin AP;Schmidt R;Scott R;Seelen MA;Shields DC;Siscovick D;Sorice R;Stanton A;Stott DJ;Sundstrom J;Swertz M;Taylor KD;Thom S;Tzoulaki I;Tzourio C;Uitterlinden AG;Volker U;Vollenweider P;Wild S;Willemsen G;Wright AF;Yao J;Theriault S;Conen D;John A;Sever P;Debette S;Mook-Kanamori DO;Zeggini E;Spector TD;van der Harst P;Palmer CNA;Vergnaud AC;Loos RJF;Polasek O;Starr JM;Girotto G;Hayward C;Kooner JS;Lindgren CM;Vitart V;Samani NJ;Tuomilehto J;Gyllensten U;Knekt P;Deary IJ;Ciullo M;Elosua R;Keavney BD;Hicks AA;Scott RA;Gasparini P;Laan M;Liu YM;Watkins H;Hartman CA;Salomaa V;Toniolo D;Perola M;Wilson JF;Schmidt H;Zhao JH;Lehtimaki T;van Duijn CM;Gudnason V;Psaty BM;Peters A;Rettig R;James A;Jukema JW;Strachan DP;Palmas W;Metspalu A;Ingelsson E;Boomsma DI;Franco OH;Bochud M;Newton-Cheh C;Munroe PB;Elliott P;Chasman DI;Chakravarti A;Knight J;Morris AP;Levy D;Tobin MD;Snieder H;Caulfield MJ;Ehret GB

2017

Abstract

Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

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				Settore MEDS-24/A - Statistica medica
			
	Data di pubblicazione
	
				2017
			
	Rivista in ANCE
	
				NATURE GENETICS
			
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				https://dx.doi.org/10.1038/ng.3768
			
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