Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.

Research output: Contribution to journalArticle

Standard

Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci. / Tragante, Vinicius; Barnes, Michael R; Ganesh, Santhi K; Lanktree, Matthew B; Guo, Wei; Franceschini, Nora; Smith, Erin N; Johnson, Toby; Holmes, Michael V; Padmanabhan, Sandosh; Karczewski, Konrad J; Almoguera, Berta; Barnard, John; Baumert, Jens; Chang, Yen-Pei Christy; Elbers, Clara C; Farrall, Martin; Fischer, Mary E; Gaunt, Tom R; Gho, Johannes M I H; Gieger, Christian; Goel, Anuj; Gong, Yan; Isaacs, Aaron; Kleber, Marcus E; Leach, Irene Mateo; McDonough, Caitrin W; Meijs, Matthijs F L; Melander, Olle; Nelson, Christopher P; Nolte, Ilja M; Pankratz, Nathan; Price, Tom S; Shaffer, Jonathan; Shah, Sonia; Tomaszewski, Maciej; van der Most, Peter J; Van Iperen, Erik P A; Vonk, Judith M; Witkowska, Kate; Wong, Caroline O L; Zhang, Li; Beitelshees, Amber L; Berenson, Gerald S; Bhatt, Deepak L; Brown, Morris; Burt, Amber; Cooper-Dehoff, Rhonda M; Connell, John M; Cruickshanks, Karen J; Curtis, Sean P; Davey-Smith, George; Delles, Christian; Gansevoort, Ron T; Guo, Xiuqing; Haiqing, Shen; Hastie, Claire E; Hofker, Marten H; Hovingh, G Kees; Kim, Daniel S; Kirkland, Susan A; Klein, Barbara E; Klein, Ronald; Li, Yun R; Maiwald, Steffi; Newton-Cheh, Christopher; O'Brien, Eoin T; Onland-Moret, N Charlotte; Palmas, Walter; Parsa, Afshin; Penninx, Brenda W; Pettinger, Mary; Vasan, Ramachandran S; Ranchalis, Jane E; M Ridker, Paul; Rose, Lynda M; Sever, Peter; Shimbo, Daichi; Steele, Laura; Stolk, Ronald P; Thorand, Barbara; Trip, Mieke D; van Duijn, Cornelia M; Verschuren, W Monique; Wijmenga, Cisca; Wyatt, Sharon; Young, J Hunter; Zwinderman, Aeilko H; Bezzina, Connie R; Boerwinkle, Eric; Casas, Juan P; Caulfield, Mark J; Chakravarti, Aravinda; Chasman, Daniel I; Davidson, Karina W; Doevendans, Pieter A; Dominiczak, Anna F; Fitzgerald, Garret A; Gums, John G; Fornage, Myriam; Hakonarson, Hakon; Halder, Indrani; Hillege, Hans L; Illig, Thomas; Jarvik, Gail P; Johnson, Julie A; Kastelein, John J P; Koenig, Wolfgang; Kumari, Meena; März, Winfried; Murray, Sarah S; O'Connell, Jeffery R; Oldehinkel, Albertine J; Pankow, James S; Rader, Daniel J; Redline, Susan; Reilly, Muredach P; Schadt, Eric E; Kottke-Marchant, Kandice; Snieder, Harold; Snyder, Michael; Stanton, Alice V; Tobin, Martin D; Uitterlinden, André G; van der Harst, Pim; van der Schouw, Yvonne T; Samani, Nilesh J; Watkins, Hugh; Johnson, Andrew D; Reiner, Alex P; Zhu, Xiaofeng; de Bakker, Paul I W; Levy, Daniel; Asselbergs, Folkert W; Munroe, Patricia B; Keating, Brendan J.

In: American Journal of Human Genetics, Vol. 94, No. 3, 2014, p. 349-360.

Research output: Contribution to journalArticle

Harvard

Tragante, V, Barnes, MR, Ganesh, SK, Lanktree, MB, Guo, W, Franceschini, N, Smith, EN, Johnson, T, Holmes, MV, Padmanabhan, S, Karczewski, KJ, Almoguera, B, Barnard, J, Baumert, J, Chang, Y-PC, Elbers, CC, Farrall, M, Fischer, ME, Gaunt, TR, Gho, JMIH, Gieger, C, Goel, A, Gong, Y, Isaacs, A, Kleber, ME, Leach, IM, McDonough, CW, Meijs, MFL, Melander, O, Nelson, CP, Nolte, IM, Pankratz, N, Price, TS, Shaffer, J, Shah, S, Tomaszewski, M, van der Most, PJ, Van Iperen, EPA, Vonk, JM, Witkowska, K, Wong, COL, Zhang, L, Beitelshees, AL, Berenson, GS, Bhatt, DL, Brown, M, Burt, A, Cooper-Dehoff, RM, Connell, JM, Cruickshanks, KJ, Curtis, SP, Davey-Smith, G, Delles, C, Gansevoort, RT, Guo, X, Haiqing, S, Hastie, CE, Hofker, MH, Hovingh, GK, Kim, DS, Kirkland, SA, Klein, BE, Klein, R, Li, YR, Maiwald, S, Newton-Cheh, C, O'Brien, ET, Onland-Moret, NC, Palmas, W, Parsa, A, Penninx, BW, Pettinger, M, Vasan, RS, Ranchalis, JE, M Ridker, P, Rose, LM, Sever, P, Shimbo, D, Steele, L, Stolk, RP, Thorand, B, Trip, MD, van Duijn, CM, Verschuren, WM, Wijmenga, C, Wyatt, S, Young, JH, Zwinderman, AH, Bezzina, CR, Boerwinkle, E, Casas, JP, Caulfield, MJ, Chakravarti, A, Chasman, DI, Davidson, KW, Doevendans, PA, Dominiczak, AF, Fitzgerald, GA, Gums, JG, Fornage, M, Hakonarson, H, Halder, I, Hillege, HL, Illig, T, Jarvik, GP, Johnson, JA, Kastelein, JJP, Koenig, W, Kumari, M, März, W, Murray, SS, O'Connell, JR, Oldehinkel, AJ, Pankow, JS, Rader, DJ, Redline, S, Reilly, MP, Schadt, EE, Kottke-Marchant, K, Snieder, H, Snyder, M, Stanton, AV, Tobin, MD, Uitterlinden, AG, van der Harst, P, van der Schouw, YT, Samani, NJ, Watkins, H, Johnson, AD, Reiner, AP, Zhu, X, de Bakker, PIW, Levy, D, Asselbergs, FW, Munroe, PB & Keating, BJ 2014, 'Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.', American Journal of Human Genetics, vol. 94, no. 3, pp. 349-360. https://doi.org/10.1016/j.ajhg.2013.12.016

APA

Tragante, V., Barnes, M. R., Ganesh, S. K., Lanktree, M. B., Guo, W., Franceschini, N., ... Keating, B. J. (2014). Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci. American Journal of Human Genetics, 94(3), 349-360. https://doi.org/10.1016/j.ajhg.2013.12.016

CBE

Tragante V, Barnes MR, Ganesh SK, Lanktree MB, Guo W, Franceschini N, Smith EN, Johnson T, Holmes MV, Padmanabhan S, Karczewski KJ, Almoguera B, Barnard J, Baumert J, Chang Y-PC, Elbers CC, Farrall M, Fischer ME, Gaunt TR, Gho JMIH, Gieger C, Goel A, Gong Y, Isaacs A, Kleber ME, Leach IM, McDonough CW, Meijs MFL, Melander O, Nelson CP, Nolte IM, Pankratz N, Price TS, Shaffer J, Shah S, Tomaszewski M, van der Most PJ, Van Iperen EPA, Vonk JM, Witkowska K, Wong COL, Zhang L, Beitelshees AL, Berenson GS, Bhatt DL, Brown M, Burt A, Cooper-Dehoff RM, Connell JM, Cruickshanks KJ, Curtis SP, Davey-Smith G, Delles C, Gansevoort RT, Guo X, Haiqing S, Hastie CE, Hofker MH, Hovingh GK, Kim DS, Kirkland SA, Klein BE, Klein R, Li YR, Maiwald S, Newton-Cheh C, O'Brien ET, Onland-Moret NC, Palmas W, Parsa A, Penninx BW, Pettinger M, Vasan RS, Ranchalis JE, M Ridker P, Rose LM, Sever P, Shimbo D, Steele L, Stolk RP, Thorand B, Trip MD, van Duijn CM, Verschuren WM, Wijmenga C, Wyatt S, Young JH, Zwinderman AH, Bezzina CR, Boerwinkle E, Casas JP, Caulfield MJ, Chakravarti A, Chasman DI, Davidson KW, Doevendans PA, Dominiczak AF, Fitzgerald GA, Gums JG, Fornage M, Hakonarson H, Halder I, Hillege HL, Illig T, Jarvik GP, Johnson JA, Kastelein JJP, Koenig W, Kumari M, März W, Murray SS, O'Connell JR, Oldehinkel AJ, Pankow JS, Rader DJ, Redline S, Reilly MP, Schadt EE, Kottke-Marchant K, Snieder H, Snyder M, Stanton AV, Tobin MD, Uitterlinden AG, van der Harst P, van der Schouw YT, Samani NJ, Watkins H, Johnson AD, Reiner AP, Zhu X, de Bakker PIW, Levy D, Asselbergs FW, Munroe PB, Keating BJ. 2014. Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci. American Journal of Human Genetics. 94(3):349-360. https://doi.org/10.1016/j.ajhg.2013.12.016

MLA

Vancouver

Author

Tragante, Vinicius ; Barnes, Michael R ; Ganesh, Santhi K ; Lanktree, Matthew B ; Guo, Wei ; Franceschini, Nora ; Smith, Erin N ; Johnson, Toby ; Holmes, Michael V ; Padmanabhan, Sandosh ; Karczewski, Konrad J ; Almoguera, Berta ; Barnard, John ; Baumert, Jens ; Chang, Yen-Pei Christy ; Elbers, Clara C ; Farrall, Martin ; Fischer, Mary E ; Gaunt, Tom R ; Gho, Johannes M I H ; Gieger, Christian ; Goel, Anuj ; Gong, Yan ; Isaacs, Aaron ; Kleber, Marcus E ; Leach, Irene Mateo ; McDonough, Caitrin W ; Meijs, Matthijs F L ; Melander, Olle ; Nelson, Christopher P ; Nolte, Ilja M ; Pankratz, Nathan ; Price, Tom S ; Shaffer, Jonathan ; Shah, Sonia ; Tomaszewski, Maciej ; van der Most, Peter J ; Van Iperen, Erik P A ; Vonk, Judith M ; Witkowska, Kate ; Wong, Caroline O L ; Zhang, Li ; Beitelshees, Amber L ; Berenson, Gerald S ; Bhatt, Deepak L ; Brown, Morris ; Burt, Amber ; Cooper-Dehoff, Rhonda M ; Connell, John M ; Cruickshanks, Karen J ; Curtis, Sean P ; Davey-Smith, George ; Delles, Christian ; Gansevoort, Ron T ; Guo, Xiuqing ; Haiqing, Shen ; Hastie, Claire E ; Hofker, Marten H ; Hovingh, G Kees ; Kim, Daniel S ; Kirkland, Susan A ; Klein, Barbara E ; Klein, Ronald ; Li, Yun R ; Maiwald, Steffi ; Newton-Cheh, Christopher ; O'Brien, Eoin T ; Onland-Moret, N Charlotte ; Palmas, Walter ; Parsa, Afshin ; Penninx, Brenda W ; Pettinger, Mary ; Vasan, Ramachandran S ; Ranchalis, Jane E ; M Ridker, Paul ; Rose, Lynda M ; Sever, Peter ; Shimbo, Daichi ; Steele, Laura ; Stolk, Ronald P ; Thorand, Barbara ; Trip, Mieke D ; van Duijn, Cornelia M ; Verschuren, W Monique ; Wijmenga, Cisca ; Wyatt, Sharon ; Young, J Hunter ; Zwinderman, Aeilko H ; Bezzina, Connie R ; Boerwinkle, Eric ; Casas, Juan P ; Caulfield, Mark J ; Chakravarti, Aravinda ; Chasman, Daniel I ; Davidson, Karina W ; Doevendans, Pieter A ; Dominiczak, Anna F ; Fitzgerald, Garret A ; Gums, John G ; Fornage, Myriam ; Hakonarson, Hakon ; Halder, Indrani ; Hillege, Hans L ; Illig, Thomas ; Jarvik, Gail P ; Johnson, Julie A ; Kastelein, John J P ; Koenig, Wolfgang ; Kumari, Meena ; März, Winfried ; Murray, Sarah S ; O'Connell, Jeffery R ; Oldehinkel, Albertine J ; Pankow, James S ; Rader, Daniel J ; Redline, Susan ; Reilly, Muredach P ; Schadt, Eric E ; Kottke-Marchant, Kandice ; Snieder, Harold ; Snyder, Michael ; Stanton, Alice V ; Tobin, Martin D ; Uitterlinden, André G ; van der Harst, Pim ; van der Schouw, Yvonne T ; Samani, Nilesh J ; Watkins, Hugh ; Johnson, Andrew D ; Reiner, Alex P ; Zhu, Xiaofeng ; de Bakker, Paul I W ; Levy, Daniel ; Asselbergs, Folkert W ; Munroe, Patricia B ; Keating, Brendan J. / Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci. In: American Journal of Human Genetics. 2014 ; Vol. 94, No. 3. pp. 349-360.

RIS

TY - JOUR

T1 - Gene-centric Meta-analysis in 87,736 Individuals of European Ancestry Identifies Multiple Blood-Pressure-Related Loci.

AU - Tragante, Vinicius

AU - Barnes, Michael R

AU - Ganesh, Santhi K

AU - Lanktree, Matthew B

AU - Guo, Wei

AU - Franceschini, Nora

AU - Smith, Erin N

AU - Johnson, Toby

AU - Holmes, Michael V

AU - Padmanabhan, Sandosh

AU - Karczewski, Konrad J

AU - Almoguera, Berta

AU - Barnard, John

AU - Baumert, Jens

AU - Chang, Yen-Pei Christy

AU - Elbers, Clara C

AU - Farrall, Martin

AU - Fischer, Mary E

AU - Gaunt, Tom R

AU - Gho, Johannes M I H

AU - Gieger, Christian

AU - Goel, Anuj

AU - Gong, Yan

AU - Isaacs, Aaron

AU - Kleber, Marcus E

AU - Leach, Irene Mateo

AU - McDonough, Caitrin W

AU - Meijs, Matthijs F L

AU - Melander, Olle

AU - Nelson, Christopher P

AU - Nolte, Ilja M

AU - Pankratz, Nathan

AU - Price, Tom S

AU - Shaffer, Jonathan

AU - Shah, Sonia

AU - Tomaszewski, Maciej

AU - van der Most, Peter J

AU - Van Iperen, Erik P A

AU - Vonk, Judith M

AU - Witkowska, Kate

AU - Wong, Caroline O L

AU - Zhang, Li

AU - Beitelshees, Amber L

AU - Berenson, Gerald S

AU - Bhatt, Deepak L

AU - Brown, Morris

AU - Burt, Amber

AU - Cooper-Dehoff, Rhonda M

AU - Connell, John M

AU - Cruickshanks, Karen J

AU - Curtis, Sean P

AU - Davey-Smith, George

AU - Delles, Christian

AU - Gansevoort, Ron T

AU - Guo, Xiuqing

AU - Haiqing, Shen

AU - Hastie, Claire E

AU - Hofker, Marten H

AU - Hovingh, G Kees

AU - Kim, Daniel S

AU - Kirkland, Susan A

AU - Klein, Barbara E

AU - Klein, Ronald

AU - Li, Yun R

AU - Maiwald, Steffi

AU - Newton-Cheh, Christopher

AU - O'Brien, Eoin T

AU - Onland-Moret, N Charlotte

AU - Palmas, Walter

AU - Parsa, Afshin

AU - Penninx, Brenda W

AU - Pettinger, Mary

AU - Vasan, Ramachandran S

AU - Ranchalis, Jane E

AU - M Ridker, Paul

AU - Rose, Lynda M

AU - Sever, Peter

AU - Shimbo, Daichi

AU - Steele, Laura

AU - Stolk, Ronald P

AU - Thorand, Barbara

AU - Trip, Mieke D

AU - van Duijn, Cornelia M

AU - Verschuren, W Monique

AU - Wijmenga, Cisca

AU - Wyatt, Sharon

AU - Young, J Hunter

AU - Zwinderman, Aeilko H

AU - Bezzina, Connie R

AU - Boerwinkle, Eric

AU - Casas, Juan P

AU - Caulfield, Mark J

AU - Chakravarti, Aravinda

AU - Chasman, Daniel I

AU - Davidson, Karina W

AU - Doevendans, Pieter A

AU - Dominiczak, Anna F

AU - Fitzgerald, Garret A

AU - Gums, John G

AU - Fornage, Myriam

AU - Hakonarson, Hakon

AU - Halder, Indrani

AU - Hillege, Hans L

AU - Illig, Thomas

AU - Jarvik, Gail P

AU - Johnson, Julie A

AU - Kastelein, John J P

AU - Koenig, Wolfgang

AU - Kumari, Meena

AU - März, Winfried

AU - Murray, Sarah S

AU - O'Connell, Jeffery R

AU - Oldehinkel, Albertine J

AU - Pankow, James S

AU - Rader, Daniel J

AU - Redline, Susan

AU - Reilly, Muredach P

AU - Schadt, Eric E

AU - Kottke-Marchant, Kandice

AU - Snieder, Harold

AU - Snyder, Michael

AU - Stanton, Alice V

AU - Tobin, Martin D

AU - Uitterlinden, André G

AU - van der Harst, Pim

AU - van der Schouw, Yvonne T

AU - Samani, Nilesh J

AU - Watkins, Hugh

AU - Johnson, Andrew D

AU - Reiner, Alex P

AU - Zhu, Xiaofeng

AU - de Bakker, Paul I W

AU - Levy, Daniel

AU - Asselbergs, Folkert W

AU - Munroe, Patricia B

AU - Keating, Brendan J

PY - 2014

Y1 - 2014

N2 - Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

AB - Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.

U2 - 10.1016/j.ajhg.2013.12.016

DO - 10.1016/j.ajhg.2013.12.016

M3 - Article

VL - 94

SP - 349

EP - 360

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -