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

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... Full description

Journal Title: Liang J., T. H. Le, D. R. V. Edwards, B. O. Tayo, K. J. Gaulton, J. A. Smith, Y. Lu, et al. 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. doi:10.1371/journal.pgen.1006728. http://dx.doi.org/10.1371/journal.pgen.1006728.
Main Author: Liang, Jingjing
Other Authors: 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 R. , 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
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: DOI: 10.1371/journal.pgen.1006728
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title: Single-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations
format: Article
creator:
  • 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 R.
  • 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
subjects:
  • Medicine And Health Sciences
  • Vascular Medicine
  • Blood Pressure
  • Hypertension
  • Biology And Life Sciences
  • Anatomy
  • Renal System
  • Kidneys
  • Genetics
  • Genetic Loci
  • Computational Biology
  • Genome Analysis
  • Genome-Wide Association Studies
  • Genomics
  • Human Genetics
  • Gene Expression
  • People And Places
  • Population Groupings
  • Ethnicities
  • Africans
  • Animal Genomics
  • Mammalian Genomics
  • Mathematical And Statistical Techniques
  • Statistical Methods
  • Meta-Analysis
  • Physical Sciences
  • Mathematics
  • Statistics (Mathematics)
ispartof: Liang, J., T. H. Le, D. R. V. Edwards, B. O. Tayo, K. J. Gaulton, J. A. Smith, Y. Lu, et al. 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. doi:10.1371/journal.pgen.1006728. http://dx.doi.org/10.1371/journal.pgen.1006728.
description: 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.
language: eng
source:
identifier: DOI: 10.1371/journal.pgen.1006728
fulltext: fulltext_linktorsrc
url: Link


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titleSingle-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations
creatorLiang, 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 R. ; 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
ispartofLiang, J., T. H. Le, D. R. V. Edwards, B. O. Tayo, K. J. Gaulton, J. A. Smith, Y. Lu, et al. 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. doi:10.1371/journal.pgen.1006728. http://dx.doi.org/10.1371/journal.pgen.1006728.
identifierDOI: 10.1371/journal.pgen.1006728
subjectMedicine And Health Sciences ; Vascular Medicine ; Blood Pressure ; Hypertension ; Biology And Life Sciences ; Anatomy ; Renal System ; Kidneys ; Genetics ; Genetic Loci ; Computational Biology ; Genome Analysis ; Genome-Wide Association Studies ; Genomics ; Human Genetics ; Gene Expression ; People And Places ; Population Groupings ; Ethnicities ; Africans ; Animal Genomics ; Mammalian Genomics ; Mathematical And Statistical Techniques ; Statistical Methods ; Meta-Analysis ; Physical Sciences ; Mathematics ; Statistics (Mathematics)
descriptionHypertension 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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0Liang, Jingjing
1Le, Thu H.
2Edwards, Digna R. Velez
3Tayo, Bamidele O.
4Gaulton, Kyle J.
5Smith, Jennifer A.
6Lu, Yingchang
7Jensen, Richard A.
8Chen, Guanjie
9Yanek, Lisa R.
10Schwander, Karen
11Tajuddin, Salman M.
12Sofer, Tamar
13Kim, Wonji
14Kayima, James
15McKenzie, Colin A.
16Fox, Ervin
17Nalls, Michael A.
18Young, J. Hunter
19Sun, Yan V.
20Lane, Jacqueline M.
21Cechova, Sylvia
22Zhou, Jie
23Tang, Hua
24Fornage, Myriam
25Musani, Solomon K.
26Wang, Heming
27Lee, Juyoung
28Adeyemo, Adebowale
29Dreisbach, Albert W.
30Forrester, Terrence
31Chu, Pei-Lun
32Cappola, Anne
33Evans, Michele K.
34Morrison, Alanna C.
35Martin, Lisa W.
36Wiggins, Kerri L.
37Hui, Qin
38Zhao, Wei
39Jackson, Rebecca D.
40Ware, Erin B.
41Faul, Jessica D.
42Reiner, Alex P.
43Bray, Michael
44Denny, Joshua C.
45Mosley, Thomas H.
46Palmas, Walter
47Guo, Xiuqing
48Papanicolaou, George J.
49Penman, Alan D.
50Polak, Joseph F.
51Rice, Kenneth
52Taylor, Ken D.
53Boerwinkle, Eric
54Bottinger, Erwin P.
55Liu, Kiang
56Risch, Neil
57Hunt, Steven C.
58Kooperberg, Charles
59Zonderman, Alan B.
60Laurie, Cathy C.
61Becker, Diane M.
62Cai, Jianwen
63Loos, Ruth J. F.
64Psaty, Bruce M.
65Weir, David R.
66Kardia, Sharon L. R.
67Arnett, Donna K.
68Won, Sungho
69Edwards, Todd L.
70Redline, Susan
71Cooper, Richard S.
72Rao, D. C.
73Rotter, Jerome I.
74Rotimi, Charles
75Levy, Daniel
76Chakravarti, Aravinda
77Zhu, Xiaofeng
78Franceschini, Nora
titleSingle-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations
descriptionHypertension 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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0Medicine and Health Sciences
1Vascular Medicine
2Blood Pressure
3Hypertension
4Biology and Life Sciences
5Anatomy
6Renal System
7Kidneys
8Genetics
9Genetic Loci
10Computational Biology
11Genome Analysis
12Genome-Wide Association Studies
13Genomics
14Human Genetics
15Gene Expression
16People and Places
17Population Groupings
18Ethnicities
19Africans
20Animal Genomics
21Mammalian Genomics
22Mathematical and Statistical Techniques
23Statistical Methods
24Meta-Analysis
25Physical Sciences
26Mathematics
27Statistics (Mathematics)
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310.1371/journal.pgen.1006728
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titleSingle-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations
authorLiang, 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 R. ; 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
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9Genetic Loci
10Computational Biology
11Genome Analysis
12Genome-Wide Association Studies
13Genomics
14Human Genetics
15Gene Expression
16People And Places
17Population Groupings
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20Animal Genomics
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0Liang, Jingjing
1Le, Thu H
2Edwards, Digna R. Velez
3Tayo, Bamidele O
4Gaulton, Kyle J
5Smith, Jennifer A
6Lu, Yingchang
7Jensen, Richard A
8Chen, Guanjie
9Yanek, Lisa R
10Schwander, Karen
11Tajuddin, Salman M
12Sofer, Tamar
13Kim, Wonji
14Kayima, James
15McKenzie, Colin A
16Fox, Ervin
17Nalls, Michael A
18Young, J. Hunter
19Sun, Yan V
20Lane, Jacqueline M
21Cechova, Sylvia
22Zhou, Jie
23Tang, Hua
24Fornage, Myriam
25Musani, Solomon K
26Wang, Heming
27Lee, Juyoung
28Adeyemo, Adebowale
29Dreisbach, Albert W
30Forrester, Terrence
31Chu, Pei-Lun
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33Evans, Michele K
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77Nora
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1Le, Thu H.
2Edwards, Digna R. Velez
3Tayo, Bamidele O.
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6Lu, Yingchang
7Jensen, Richard A.
8Chen, Guanjie
9Yanek, Lisa R.
10Schwander, Karen
11Tajuddin, Salman M.
12Sofer, Tamar
13Kim, Wonji
14Kayima, James
15McKenzie, Colin A.
16Fox, Ervin
17Nalls, Michael A.
18Young, J. Hunter
19Sun, Yan V.
20Lane, Jacqueline M.
21Cechova, Sylvia
22Zhou, Jie
23Tang, Hua
24Fornage, Myriam
25Musani, Solomon K.
26Wang, Heming
27Lee, Juyoung
28Adeyemo, Adebowale
29Dreisbach, Albert W.
30Forrester, Terrence
31Chu, Pei-Lun
32Cappola, Anne
33Evans, Michele K.
34Morrison, Alanna C.
35Martin, Lisa W.
36Wiggins, Kerri L.
37Hui, Qin
38Zhao, Wei
39Jackson, Rebecca D.
40Ware, Erin B.
41Faul, Jessica D.
42Reiner, Alex P.
43Bray, Michael
44Denny, Joshua C.
45Mosley, Thomas H.
46Palmas, Walter
47Guo, Xiuqing
48Papanicolaou, George J.
49Penman, Alan D.
50Polak, Joseph F.
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53Boerwinkle, Eric
54Bottinger, Erwin P.
55Liu, Kiang
56Risch, Neil
57Hunt, Steven C.
58Kooperberg, Charles
59Zonderman, Alan B.
60Laurie, Cathy C.
61Becker, Diane M.
62Cai, Jianwen
63Loos, Ruth J. F.
64Psaty, Bruce M.
65Weir, David R.
66Kardia, Sharon L. R.
67Arnett, Donna K.
68Won, Sungho
69Edwards, Todd L.
70Redline, Susan
71Cooper, Richard S.
72Rao, D. C.
73Rotter, Jerome I.
74Rotimi, Charles
75Levy, Daniel
76Chakravarti, Aravinda
77Zhu, Xiaofeng
78Franceschini, Nora
atitleSingle-trait and multi-trait genome-wide association analyses identify novel loci for blood pressure in African-ancestry populations
jtitlePLoS Genetics
date2017
risdate2017
genrearticle
ristypeJOUR
abstractHypertension 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.
pubPublic Library of Science
doi10.1371/journal.pgen.1006728
urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446189/pdf/
pagese1006728
volume13
orcidid0000-0002-3575-5468
issue5
issn15537390
eissn15537404
oafree_for_read