Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations

Nora Franceschini, Ervin Fox, Zhaogong Zhang, Todd L. Edwards, Michael A. Nalls, Yun Ju Sung, Bamidele O. Tayo, Yan V. Sun, Omri Gottesman, Adebawole Adeyemo, Andrew D. Johnson, J. Hunter Young, Ken Rice, Qing Duan, Fang Chen, Yun Li, Hua Tang, Myriam Fornage, Keith L. Keene, Jeanette S. Andrews & 86 others Jennifer A. Smith, Jessica D. Faul, Zhang Guangfa, Wei Guo, Yu Liu, Sarah S. Murray, Solomon K. Musani, Sathanur Srinivasan, Digna R. Velez Edwards, Heming Wang, Lewis C. Becker, Pascal Bovet, Murielle Bochud, Ulrich Broeckel, Michel Burnier, Cara Carty, Daniel I. Chasman, Georg Ehret, Wei Min Chen, Guanjie Chen, Wei Chan, Jingzhong Ding, Albert W. Dreisbach, Michele K. Evans, Xiuqing Guo, Melissa E. Garcia, Rich Jensen, Margaux F. Keller, Guillaume Lettre, Vaneet Lotay, Lisa W. Martin, Jason H. Moore, Alanna C. Morrison, Thomas H. Mosley, Adesola Ogunniyi, Walter Palmas, George Papanicolaou, Alan Penman, Joseph F. Polak, Paul M. Ridker, Babatunde Salako, Andrew B. Singleton, Daniel Shriner, Kent D. Taylor, Ramachandran Vasan, Kerri Wiggins, Scott M. Williams, Lisa R. Yanek, Wei Zhao, Alan B. Zonderman, Diane M. Becker, Gerald Berenson, Eric Boerwinkle, Erwin Bottinger, Mary Cushman, Charles Eaton, Fredrik Nyberg, Gerardo Heiss, Joel N. Hirschhron, Virginia J. Howard, Konrad J. Karczewsk, Matthew B. Lanktree, Kiang Liu, Yongmei Liu, Ruth Loos, Karen Margolis, Michael Snyder, Bruce M. Psaty, Nicholas J. Schork, David R. Weir, Charles N. Rotimi, Michele M. Sale, Tamara Harris, Sharon L R Kardia, Steven Hunt, Donna Arnett, Susan Redline, Richard S. Cooper, Neil J. Risch, D. C. Rao, Jerome I. Rotter, Aravinda Chakravarti, Alex P. Reiner, Daniel Levy, Brendan J. Keating, Xiaofeng Zhu

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10-8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

Original languageEnglish
Pages (from-to)545-554
Number of pages10
JournalAmerican Journal of Human Genetics
Volume93
Issue number3
DOIs
Publication statusPublished - 5 Sep 2013
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Blood Pressure
Population
Genes
Meta-Analysis
Ethnic Groups
African Americans
Cardiovascular Diseases
Genome
Hypertension

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations. / Franceschini, Nora; Fox, Ervin; Zhang, Zhaogong; Edwards, Todd L.; Nalls, Michael A.; Sung, Yun Ju; Tayo, Bamidele O.; Sun, Yan V.; Gottesman, Omri; Adeyemo, Adebawole; Johnson, Andrew D.; Young, J. Hunter; Rice, Ken; Duan, Qing; Chen, Fang; Li, Yun; Tang, Hua; Fornage, Myriam; Keene, Keith L.; Andrews, Jeanette S.; Smith, Jennifer A.; Faul, Jessica D.; Guangfa, Zhang; Guo, Wei; Liu, Yu; Murray, Sarah S.; Musani, Solomon K.; Srinivasan, Sathanur; Velez Edwards, Digna R.; Wang, Heming; Becker, Lewis C.; Bovet, Pascal; Bochud, Murielle; Broeckel, Ulrich; Burnier, Michel; Carty, Cara; Chasman, Daniel I.; Ehret, Georg; Chen, Wei Min; Chen, Guanjie; Chan, Wei; Ding, Jingzhong; Dreisbach, Albert W.; Evans, Michele K.; Guo, Xiuqing; Garcia, Melissa E.; Jensen, Rich; Keller, Margaux F.; Lettre, Guillaume; Lotay, Vaneet; Martin, Lisa W.; Moore, Jason H.; Morrison, Alanna C.; Mosley, Thomas H.; Ogunniyi, Adesola; Palmas, Walter; Papanicolaou, George; Penman, Alan; Polak, Joseph F.; Ridker, Paul M.; Salako, Babatunde; Singleton, Andrew B.; Shriner, Daniel; Taylor, Kent D.; Vasan, Ramachandran; Wiggins, Kerri; Williams, Scott M.; Yanek, Lisa R.; Zhao, Wei; Zonderman, Alan B.; Becker, Diane M.; Berenson, Gerald; Boerwinkle, Eric; Bottinger, Erwin; Cushman, Mary; Eaton, Charles; Nyberg, Fredrik; Heiss, Gerardo; Hirschhron, Joel N.; Howard, Virginia J.; Karczewsk, Konrad J.; Lanktree, Matthew B.; Liu, Kiang; Liu, Yongmei; Loos, Ruth; Margolis, Karen; Snyder, Michael; Psaty, Bruce M.; Schork, Nicholas J.; Weir, David R.; Rotimi, Charles N.; Sale, Michele M.; Harris, Tamara; Kardia, Sharon L R; Hunt, Steven; Arnett, Donna; Redline, Susan; Cooper, Richard S.; Risch, Neil J.; Rao, D. C.; Rotter, Jerome I.; Chakravarti, Aravinda; Reiner, Alex P.; Levy, Daniel; Keating, Brendan J.; Zhu, Xiaofeng.

In: American Journal of Human Genetics, Vol. 93, No. 3, 05.09.2013, p. 545-554.

Research output: Contribution to journalArticle

Franceschini, N, Fox, E, Zhang, Z, Edwards, TL, Nalls, MA, Sung, YJ, Tayo, BO, Sun, YV, Gottesman, O, Adeyemo, A, Johnson, AD, Young, JH, Rice, K, Duan, Q, Chen, F, Li, Y, Tang, H, Fornage, M, Keene, KL, Andrews, JS, Smith, JA, Faul, JD, Guangfa, Z, Guo, W, Liu, Y, Murray, SS, Musani, SK, Srinivasan, S, Velez Edwards, DR, Wang, H, Becker, LC, Bovet, P, Bochud, M, Broeckel, U, Burnier, M, Carty, C, Chasman, DI, Ehret, G, Chen, WM, Chen, G, Chan, W, Ding, J, Dreisbach, AW, Evans, MK, Guo, X, Garcia, ME, Jensen, R, Keller, MF, Lettre, G, Lotay, V, Martin, LW, Moore, JH, Morrison, AC, Mosley, TH, Ogunniyi, A, Palmas, W, Papanicolaou, G, Penman, A, Polak, JF, Ridker, PM, Salako, B, Singleton, AB, Shriner, D, Taylor, KD, Vasan, R, Wiggins, K, Williams, SM, Yanek, LR, Zhao, W, Zonderman, AB, Becker, DM, Berenson, G, Boerwinkle, E, Bottinger, E, Cushman, M, Eaton, C, Nyberg, F, Heiss, G, Hirschhron, JN, Howard, VJ, Karczewsk, KJ, Lanktree, MB, Liu, K, Liu, Y, Loos, R, Margolis, K, Snyder, M, Psaty, BM, Schork, NJ, Weir, DR, Rotimi, CN, Sale, MM, Harris, T, Kardia, SLR, Hunt, S, Arnett, D, Redline, S, Cooper, RS, Risch, NJ, Rao, DC, Rotter, JI, Chakravarti, A, Reiner, AP, Levy, D, Keating, BJ & Zhu, X 2013, 'Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations', American Journal of Human Genetics, vol. 93, no. 3, pp. 545-554. https://doi.org/10.1016/j.ajhg.2013.07.010
Franceschini, Nora ; Fox, Ervin ; Zhang, Zhaogong ; Edwards, Todd L. ; Nalls, Michael A. ; Sung, Yun Ju ; Tayo, Bamidele O. ; Sun, Yan V. ; Gottesman, Omri ; Adeyemo, Adebawole ; Johnson, Andrew D. ; Young, J. Hunter ; Rice, Ken ; Duan, Qing ; Chen, Fang ; Li, Yun ; Tang, Hua ; Fornage, Myriam ; Keene, Keith L. ; Andrews, Jeanette S. ; Smith, Jennifer A. ; Faul, Jessica D. ; Guangfa, Zhang ; Guo, Wei ; Liu, Yu ; Murray, Sarah S. ; Musani, Solomon K. ; Srinivasan, Sathanur ; Velez Edwards, Digna R. ; Wang, Heming ; Becker, Lewis C. ; Bovet, Pascal ; Bochud, Murielle ; Broeckel, Ulrich ; Burnier, Michel ; Carty, Cara ; Chasman, Daniel I. ; Ehret, Georg ; Chen, Wei Min ; Chen, Guanjie ; Chan, Wei ; Ding, Jingzhong ; Dreisbach, Albert W. ; Evans, Michele K. ; Guo, Xiuqing ; Garcia, Melissa E. ; Jensen, Rich ; Keller, Margaux F. ; Lettre, Guillaume ; Lotay, Vaneet ; Martin, Lisa W. ; Moore, Jason H. ; Morrison, Alanna C. ; Mosley, Thomas H. ; Ogunniyi, Adesola ; Palmas, Walter ; Papanicolaou, George ; Penman, Alan ; Polak, Joseph F. ; Ridker, Paul M. ; Salako, Babatunde ; Singleton, Andrew B. ; Shriner, Daniel ; Taylor, Kent D. ; Vasan, Ramachandran ; Wiggins, Kerri ; Williams, Scott M. ; Yanek, Lisa R. ; Zhao, Wei ; Zonderman, Alan B. ; Becker, Diane M. ; Berenson, Gerald ; Boerwinkle, Eric ; Bottinger, Erwin ; Cushman, Mary ; Eaton, Charles ; Nyberg, Fredrik ; Heiss, Gerardo ; Hirschhron, Joel N. ; Howard, Virginia J. ; Karczewsk, Konrad J. ; Lanktree, Matthew B. ; Liu, Kiang ; Liu, Yongmei ; Loos, Ruth ; Margolis, Karen ; Snyder, Michael ; Psaty, Bruce M. ; Schork, Nicholas J. ; Weir, David R. ; Rotimi, Charles N. ; Sale, Michele M. ; Harris, Tamara ; Kardia, Sharon L R ; Hunt, Steven ; Arnett, Donna ; Redline, Susan ; Cooper, Richard S. ; Risch, Neil J. ; Rao, D. C. ; Rotter, Jerome I. ; Chakravarti, Aravinda ; Reiner, Alex P. ; Levy, Daniel ; Keating, Brendan J. ; Zhu, Xiaofeng. / Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations. In: American Journal of Human Genetics. 2013 ; Vol. 93, No. 3. pp. 545-554.
@article{8a0a156229c045fc9d2b3da345e900f1,
title = "Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations",
abstract = "High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10-8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.",
author = "Nora Franceschini and Ervin Fox and Zhaogong Zhang and Edwards, {Todd L.} and Nalls, {Michael A.} and Sung, {Yun Ju} and Tayo, {Bamidele O.} and Sun, {Yan V.} and Omri Gottesman and Adebawole Adeyemo and Johnson, {Andrew D.} and Young, {J. Hunter} and Ken Rice and Qing Duan and Fang Chen and Yun Li and Hua Tang and Myriam Fornage and Keene, {Keith L.} and Andrews, {Jeanette S.} and Smith, {Jennifer A.} and Faul, {Jessica D.} and Zhang Guangfa and Wei Guo and Yu Liu and Murray, {Sarah S.} and Musani, {Solomon K.} and Sathanur Srinivasan and {Velez Edwards}, {Digna R.} and Heming Wang and Becker, {Lewis C.} and Pascal Bovet and Murielle Bochud and Ulrich Broeckel and Michel Burnier and Cara Carty and Chasman, {Daniel I.} and Georg Ehret and Chen, {Wei Min} and Guanjie Chen and Wei Chan and Jingzhong Ding and Dreisbach, {Albert W.} and Evans, {Michele K.} and Xiuqing Guo and Garcia, {Melissa E.} and Rich Jensen and Keller, {Margaux F.} and Guillaume Lettre and Vaneet Lotay and Martin, {Lisa W.} and Moore, {Jason H.} and Morrison, {Alanna C.} and Mosley, {Thomas H.} and Adesola Ogunniyi and Walter Palmas and George Papanicolaou and Alan Penman and Polak, {Joseph F.} and Ridker, {Paul M.} and Babatunde Salako and Singleton, {Andrew B.} and Daniel Shriner and Taylor, {Kent D.} and Ramachandran Vasan and Kerri Wiggins and Williams, {Scott M.} and Yanek, {Lisa R.} and Wei Zhao and Zonderman, {Alan B.} and Becker, {Diane M.} and Gerald Berenson and Eric Boerwinkle and Erwin Bottinger and Mary Cushman and Charles Eaton and Fredrik Nyberg and Gerardo Heiss and Hirschhron, {Joel N.} and Howard, {Virginia J.} and Karczewsk, {Konrad J.} and Lanktree, {Matthew B.} and Kiang Liu and Yongmei Liu and Ruth Loos and Karen Margolis and Michael Snyder and Psaty, {Bruce M.} and Schork, {Nicholas J.} and Weir, {David R.} and Rotimi, {Charles N.} and Sale, {Michele M.} and Tamara Harris and Kardia, {Sharon L R} and Steven Hunt and Donna Arnett and Susan Redline and Cooper, {Richard S.} and Risch, {Neil J.} and Rao, {D. C.} and Rotter, {Jerome I.} and Aravinda Chakravarti and Reiner, {Alex P.} and Daniel Levy and Keating, {Brendan J.} and Xiaofeng Zhu",
year = "2013",
month = "9",
day = "5",
doi = "10.1016/j.ajhg.2013.07.010",
language = "English",
volume = "93",
pages = "545--554",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - Genome-wide association analysis of blood-pressure traits in african-ancestry individuals reveals common associated genes in African and Non-African populations

AU - Franceschini, Nora

AU - Fox, Ervin

AU - Zhang, Zhaogong

AU - Edwards, Todd L.

AU - Nalls, Michael A.

AU - Sung, Yun Ju

AU - Tayo, Bamidele O.

AU - Sun, Yan V.

AU - Gottesman, Omri

AU - Adeyemo, Adebawole

AU - Johnson, Andrew D.

AU - Young, J. Hunter

AU - Rice, Ken

AU - Duan, Qing

AU - Chen, Fang

AU - Li, Yun

AU - Tang, Hua

AU - Fornage, Myriam

AU - Keene, Keith L.

AU - Andrews, Jeanette S.

AU - Smith, Jennifer A.

AU - Faul, Jessica D.

AU - Guangfa, Zhang

AU - Guo, Wei

AU - Liu, Yu

AU - Murray, Sarah S.

AU - Musani, Solomon K.

AU - Srinivasan, Sathanur

AU - Velez Edwards, Digna R.

AU - Wang, Heming

AU - Becker, Lewis C.

AU - Bovet, Pascal

AU - Bochud, Murielle

AU - Broeckel, Ulrich

AU - Burnier, Michel

AU - Carty, Cara

AU - Chasman, Daniel I.

AU - Ehret, Georg

AU - Chen, Wei Min

AU - Chen, Guanjie

AU - Chan, Wei

AU - Ding, Jingzhong

AU - Dreisbach, Albert W.

AU - Evans, Michele K.

AU - Guo, Xiuqing

AU - Garcia, Melissa E.

AU - Jensen, Rich

AU - Keller, Margaux F.

AU - Lettre, Guillaume

AU - Lotay, Vaneet

AU - Martin, Lisa W.

AU - Moore, Jason H.

AU - Morrison, Alanna C.

AU - Mosley, Thomas H.

AU - Ogunniyi, Adesola

AU - Palmas, Walter

AU - Papanicolaou, George

AU - Penman, Alan

AU - Polak, Joseph F.

AU - Ridker, Paul M.

AU - Salako, Babatunde

AU - Singleton, Andrew B.

AU - Shriner, Daniel

AU - Taylor, Kent D.

AU - Vasan, Ramachandran

AU - Wiggins, Kerri

AU - Williams, Scott M.

AU - Yanek, Lisa R.

AU - Zhao, Wei

AU - Zonderman, Alan B.

AU - Becker, Diane M.

AU - Berenson, Gerald

AU - Boerwinkle, Eric

AU - Bottinger, Erwin

AU - Cushman, Mary

AU - Eaton, Charles

AU - Nyberg, Fredrik

AU - Heiss, Gerardo

AU - Hirschhron, Joel N.

AU - Howard, Virginia J.

AU - Karczewsk, Konrad J.

AU - Lanktree, Matthew B.

AU - Liu, Kiang

AU - Liu, Yongmei

AU - Loos, Ruth

AU - Margolis, Karen

AU - Snyder, Michael

AU - Psaty, Bruce M.

AU - Schork, Nicholas J.

AU - Weir, David R.

AU - Rotimi, Charles N.

AU - Sale, Michele M.

AU - Harris, Tamara

AU - Kardia, Sharon L R

AU - Hunt, Steven

AU - Arnett, Donna

AU - Redline, Susan

AU - Cooper, Richard S.

AU - Risch, Neil J.

AU - Rao, D. C.

AU - Rotter, Jerome I.

AU - Chakravarti, Aravinda

AU - Reiner, Alex P.

AU - Levy, Daniel

AU - Keating, Brendan J.

AU - Zhu, Xiaofeng

PY - 2013/9/5

Y1 - 2013/9/5

N2 - High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10-8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

AB - High blood pressure (BP) is more prevalent and contributes to more severe manifestations of cardiovascular disease (CVD) in African Americans than in any other United States ethnic group. Several small African-ancestry (AA) BP genome-wide association studies (GWASs) have been published, but their findings have failed to replicate to date. We report on a large AA BP GWAS meta-analysis that includes 29,378 individuals from 19 discovery cohorts and subsequent replication in additional samples of AA (n = 10,386), European ancestry (EA) (n = 69,395), and East Asian ancestry (n = 19,601). Five loci (EVX1-HOXA, ULK4, RSPO3, PLEKHG1, and SOX6) reached genome-wide significance (p < 1.0 × 10-8) for either systolic or diastolic BP in a transethnic meta-analysis after correction for multiple testing. Three of these BP loci (EVX1-HOXA, RSPO3, and PLEKHG1) lack previous associations with BP. We also identified one independent signal in a known BP locus (SOX6) and provide evidence for fine mapping in four additional validated BP loci. We also demonstrate that validated EA BP GWAS loci, considered jointly, show significant effects in AA samples. Consequently, these findings suggest that BP loci might have universal effects across studied populations, demonstrating that multiethnic samples are an essential component in identifying, fine mapping, and understanding their trait variability.

UR - http://www.scopus.com/inward/record.url?scp=84883824600&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883824600&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2013.07.010

DO - 10.1016/j.ajhg.2013.07.010

M3 - Article

VL - 93

SP - 545

EP - 554

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -