Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

Jingjing Liang, Thu H. Le, Digna R.Velez Edwards, Bamidele O. Tayo, Kyle J. Gaulton, Jennifer A. Smith, Yingchang Lu, Richard A. Jensen, Guanjie Chen, Lisa Yanek, Karen Schwander, Salman M. Tajuddin, Tamar Sofer, Wonji Kim, James Kayima, Colin A. McKenzie, Ervin Fox, Michael A. Nalls, J Hunter Young, Yan V. SunJacqueline M. Lane, Sylvia Cechova, Jie Zhou, Hua Tang, Myriam Fornage, Solomon K. Musani, Heming Wang, Juyoung Lee, Adebowale Adeyemo, Albert W. Dreisbach, Terrence Forrester, Pei Lun Chu, Anne Cappola, Michele K. Evans, Alanna C. Morrison, Lisa W. Martin, Kerri L. Wiggins, Qin Hui, Wei Zhao, Rebecca D. Jackson, Erin B. Ware, Jessica D. Faul, Alex P. Reiner, Michael Bray, Joshua C. Denny, Thomas H. Mosley, Walter Palmas, Xiuqing Guo, George J. Papanicolaou, Alan D. Penman, Joseph F. Polak, Kenneth Rice, Ken D. Taylor, Eric Boerwinkle, Erwin P. Bottinger, Kiang Liu, Neil Risch, Steven C. Hunt, Charles Kooperberg, Alan B. Zonderman, Cathy C. Laurie, Diane M Becker, Jianwen Cai, Ruth J.F. Loos, Bruce M. Psaty, David R. Weir, Sharon L.R. Kardia, Donna K. Arnett, Sungho Won, Todd L. Edwards, Susan Redline, Richard S. Cooper, D. C. Rao, Jerome I. Rotter, Charles Rotimi, Daniel Levy, Aravinda Chakravarti, Xiaofeng Zhu, Nora Franceschini

Research output: Contribution to journalArticle

Abstract

Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

Original languageEnglish (US)
Article numbere1006728
JournalPLoS Genetics
Volume13
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

hypertension
Genome-Wide Association Study
ancestry
blood pressure
genome
blood
Blood Pressure
Hypertension
loci
Population
gene
Kidney
genes
angiotensin II
diastolic blood pressure
disability
Biological Factors
systolic blood pressure
kidney cells
blood vessels

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

Liang, J., Le, T. H., Edwards, D. R. V., Tayo, B. O., Gaulton, K. J., Smith, J. A., ... Franceschini, N. (2017). Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations. PLoS Genetics, 13(5), [e1006728]. https://doi.org/10.1371/journal.pgen.1006728

Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations. / Liang, Jingjing; Le, Thu H.; Edwards, Digna R.Velez; Tayo, Bamidele O.; Gaulton, Kyle J.; Smith, Jennifer A.; Lu, Yingchang; Jensen, Richard A.; Chen, Guanjie; Yanek, Lisa; Schwander, Karen; Tajuddin, Salman M.; Sofer, Tamar; Kim, Wonji; Kayima, James; McKenzie, Colin A.; Fox, Ervin; Nalls, Michael A.; Young, J Hunter; Sun, Yan V.; Lane, Jacqueline M.; Cechova, Sylvia; Zhou, Jie; Tang, Hua; Fornage, Myriam; Musani, Solomon K.; Wang, Heming; Lee, Juyoung; Adeyemo, Adebowale; Dreisbach, Albert W.; Forrester, Terrence; Chu, Pei Lun; Cappola, Anne; Evans, Michele K.; Morrison, Alanna C.; Martin, Lisa W.; Wiggins, Kerri L.; Hui, Qin; Zhao, Wei; Jackson, Rebecca D.; Ware, Erin B.; Faul, Jessica D.; Reiner, Alex P.; Bray, Michael; Denny, Joshua C.; Mosley, Thomas H.; Palmas, Walter; Guo, Xiuqing; Papanicolaou, George J.; Penman, Alan D.; Polak, Joseph F.; Rice, Kenneth; Taylor, Ken D.; Boerwinkle, Eric; Bottinger, Erwin P.; Liu, Kiang; Risch, Neil; Hunt, Steven C.; Kooperberg, Charles; Zonderman, Alan B.; Laurie, Cathy C.; Becker, Diane M; Cai, Jianwen; Loos, Ruth J.F.; Psaty, Bruce M.; Weir, David R.; Kardia, Sharon L.R.; Arnett, Donna K.; Won, Sungho; Edwards, Todd L.; Redline, Susan; Cooper, Richard S.; Rao, D. C.; Rotter, Jerome I.; Rotimi, Charles; Levy, Daniel; Chakravarti, Aravinda; Zhu, Xiaofeng; Franceschini, Nora.

In: PLoS Genetics, Vol. 13, No. 5, e1006728, 01.05.2017.

Research output: Contribution to journalArticle

Liang, J, Le, TH, Edwards, DRV, Tayo, BO, Gaulton, KJ, Smith, JA, Lu, Y, Jensen, RA, Chen, G, Yanek, L, Schwander, K, Tajuddin, SM, Sofer, T, Kim, W, Kayima, J, McKenzie, CA, Fox, E, Nalls, MA, Young, JH, Sun, YV, Lane, JM, Cechova, S, Zhou, J, Tang, H, Fornage, M, Musani, SK, Wang, H, Lee, J, Adeyemo, A, Dreisbach, AW, Forrester, T, Chu, PL, Cappola, A, Evans, MK, Morrison, AC, Martin, LW, Wiggins, KL, Hui, Q, Zhao, W, Jackson, RD, Ware, EB, Faul, JD, Reiner, AP, Bray, M, Denny, JC, Mosley, TH, Palmas, W, Guo, X, Papanicolaou, GJ, Penman, AD, Polak, JF, Rice, K, Taylor, KD, Boerwinkle, E, Bottinger, EP, Liu, K, Risch, N, Hunt, SC, Kooperberg, C, Zonderman, AB, Laurie, CC, Becker, DM, Cai, J, Loos, RJF, Psaty, BM, Weir, DR, Kardia, SLR, Arnett, DK, Won, S, Edwards, TL, Redline, S, Cooper, RS, Rao, DC, Rotter, JI, Rotimi, C, Levy, D, Chakravarti, A, Zhu, X & Franceschini, N 2017, 'Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations', PLoS Genetics, vol. 13, no. 5, e1006728. https://doi.org/10.1371/journal.pgen.1006728
Liang, Jingjing ; Le, Thu H. ; Edwards, Digna R.Velez ; Tayo, Bamidele O. ; Gaulton, Kyle J. ; Smith, Jennifer A. ; Lu, Yingchang ; Jensen, Richard A. ; Chen, Guanjie ; Yanek, Lisa ; Schwander, Karen ; Tajuddin, Salman M. ; Sofer, Tamar ; Kim, Wonji ; Kayima, James ; McKenzie, Colin A. ; Fox, Ervin ; Nalls, Michael A. ; Young, J Hunter ; Sun, Yan V. ; Lane, Jacqueline M. ; Cechova, Sylvia ; Zhou, Jie ; Tang, Hua ; Fornage, Myriam ; Musani, Solomon K. ; Wang, Heming ; Lee, Juyoung ; Adeyemo, Adebowale ; Dreisbach, Albert W. ; Forrester, Terrence ; Chu, Pei Lun ; Cappola, Anne ; Evans, Michele K. ; Morrison, Alanna C. ; Martin, Lisa W. ; Wiggins, Kerri L. ; Hui, Qin ; Zhao, Wei ; Jackson, Rebecca D. ; Ware, Erin B. ; Faul, Jessica D. ; Reiner, Alex P. ; Bray, Michael ; Denny, Joshua C. ; Mosley, Thomas H. ; Palmas, Walter ; Guo, Xiuqing ; Papanicolaou, George J. ; Penman, Alan D. ; Polak, Joseph F. ; Rice, Kenneth ; Taylor, Ken D. ; Boerwinkle, Eric ; Bottinger, Erwin P. ; Liu, Kiang ; Risch, Neil ; Hunt, Steven C. ; Kooperberg, Charles ; Zonderman, Alan B. ; Laurie, Cathy C. ; Becker, Diane M ; Cai, Jianwen ; Loos, Ruth J.F. ; Psaty, Bruce M. ; Weir, David R. ; Kardia, Sharon L.R. ; Arnett, Donna K. ; Won, Sungho ; Edwards, Todd L. ; Redline, Susan ; Cooper, Richard S. ; Rao, D. C. ; Rotter, Jerome I. ; Rotimi, Charles ; Levy, Daniel ; Chakravarti, Aravinda ; Zhu, Xiaofeng ; Franceschini, Nora. / Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations. In: PLoS Genetics. 2017 ; Vol. 13, No. 5.
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abstract = "Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.",
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T1 - Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations

AU - Liang, Jingjing

AU - Le, Thu H.

AU - Edwards, Digna R.Velez

AU - Tayo, Bamidele O.

AU - Gaulton, Kyle J.

AU - Smith, Jennifer A.

AU - Lu, Yingchang

AU - Jensen, Richard A.

AU - Chen, Guanjie

AU - Yanek, Lisa

AU - Schwander, Karen

AU - Tajuddin, Salman M.

AU - Sofer, Tamar

AU - Kim, Wonji

AU - Kayima, James

AU - McKenzie, Colin A.

AU - Fox, Ervin

AU - Nalls, Michael A.

AU - Young, J Hunter

AU - Sun, Yan V.

AU - Lane, Jacqueline M.

AU - Cechova, Sylvia

AU - Zhou, Jie

AU - Tang, Hua

AU - Fornage, Myriam

AU - Musani, Solomon K.

AU - Wang, Heming

AU - Lee, Juyoung

AU - Adeyemo, Adebowale

AU - Dreisbach, Albert W.

AU - Forrester, Terrence

AU - Chu, Pei Lun

AU - Cappola, Anne

AU - Evans, Michele K.

AU - Morrison, Alanna C.

AU - Martin, Lisa W.

AU - Wiggins, Kerri L.

AU - Hui, Qin

AU - Zhao, Wei

AU - Jackson, Rebecca D.

AU - Ware, Erin B.

AU - Faul, Jessica D.

AU - Reiner, Alex P.

AU - Bray, Michael

AU - Denny, Joshua C.

AU - Mosley, Thomas H.

AU - Palmas, Walter

AU - Guo, Xiuqing

AU - Papanicolaou, George J.

AU - Penman, Alan D.

AU - Polak, Joseph F.

AU - Rice, Kenneth

AU - Taylor, Ken D.

AU - Boerwinkle, Eric

AU - Bottinger, Erwin P.

AU - Liu, Kiang

AU - Risch, Neil

AU - Hunt, Steven C.

AU - Kooperberg, Charles

AU - Zonderman, Alan B.

AU - Laurie, Cathy C.

AU - Becker, Diane M

AU - Cai, Jianwen

AU - Loos, Ruth J.F.

AU - Psaty, Bruce M.

AU - Weir, David R.

AU - Kardia, Sharon L.R.

AU - Arnett, Donna K.

AU - Won, Sungho

AU - Edwards, Todd L.

AU - Redline, Susan

AU - Cooper, Richard S.

AU - Rao, D. C.

AU - Rotter, Jerome I.

AU - Rotimi, Charles

AU - Levy, Daniel

AU - Chakravarti, Aravinda

AU - Zhu, Xiaofeng

AU - Franceschini, Nora

PY - 2017/5/1

Y1 - 2017/5/1

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AB - Hypertension is a leading cause of global disease, mortality, and disability. While individuals of African descent suffer a disproportionate burden of hypertension and its complications, they have been underrepresented in genetic studies. To identify novel susceptibility loci for blood pressure and hypertension in people of African ancestry, we performed both single and multiple-trait genome-wide association analyses. We analyzed 21 genome-wide association studies comprised of 31,968 individuals of African ancestry, and validated our results with additional 54,395 individuals from multi-ethnic studies. These analyses identified nine loci with eleven independent variants which reached genome-wide significance (P < 1.25×10−8) for either systolic and diastolic blood pressure, hypertension, or for combined traits. Single-trait analyses identified two loci (TARID/TCF21 and LLPH/TMBIM4) and multiple-trait analyses identified one novel locus (FRMD3) for blood pressure. At these three loci, as well as at GRP20/CDH17, associated variants had alleles common only in African-ancestry populations. Functional annotation showed enrichment for genes expressed in immune and kidney cells, as well as in heart and vascular cells/tissues. Experiments driven by these findings and using angiotensin-II induced hypertension in mice showed altered kidney mRNA expression of six genes, suggesting their potential role in hypertension. Our study provides new evidence for genes related to hypertension susceptibility, and the need to study African-ancestry populations in order to identify biologic factors contributing to hypertension.

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