Association of genetic variation with systolic and diastolic blood pressure among african americans: The candidate gene association resource study

Ervin R. Fox, J. Hunter Young, Yali Li, Albert W. Dreisbach, Brendan J. Keating, Solomon K. Musani, Kiang Liu, Alanna C. Morrison, Santhi Ganesh, Abdullah Kutlar, Vasan S. Ramachandran, Josef F. Polak, Richard R. Fabsitz, Daniel L. Dries, Deborah N. Farlow, Susan Redline, Adebowale Adeyemo, Joel N. Hirschorn, Yan V. Sun, Sharon B. WyattAlan D. Penman, Walter Palmas, Jerome I. Rotter, Raymond R. Townsend, Ayo P. Doumatey, Bamidele O. Tayo, Thomas H. Mosley, Helen N. Lyon, Sun J. Kang, Charles N. Rotimi, Richard S. Cooper, Nora Franceschini, J. David Curb, Lisa W. Martin, Charles B. Eaton, Sharon L.R. Kardia, Herman A. Taylor, Mark J. Caulfield, Georg B. Ehret, Toby Johnson, Aravinda Chakravarti, Xiaofeng Zhu, Daniel Levy

Research output: Contribution to journalArticle

121 Citations (Scopus)

Abstract

The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide singlenucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P = 3.6 ×10-8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P = 4.7 × 10-8). The top IBC association for SBP was rs2012318 (P = 6.4 × 10-6)) near SLC25A42 and for DBP was rs2523586 (P = 1.3 3 10-6) near HLA-B. None of the top variants replicated in additional AA (n 5 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P = 0.009; TBX3-TBX5, P = 0.03; and CSK-ULK3, P = 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. The Author 2011. Published by Oxford University Press.

Original languageEnglish (US)
Article numberddr092
Pages (from-to)2273-2284
Number of pages12
JournalHuman Molecular Genetics
Volume20
Issue number11
DOIs
StatePublished - Jun 1 2011

Fingerprint

Genetic Association Studies
African Americans
Blood Pressure
Genes
Genome-Wide Association Study
Single Nucleotide Polymorphism
Genome
HapMap Project
Genetic Loci
HLA-B Antigens

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Fox, E. R., Young, J. H., Li, Y., Dreisbach, A. W., Keating, B. J., Musani, S. K., ... Levy, D. (2011). Association of genetic variation with systolic and diastolic blood pressure among african americans: The candidate gene association resource study. Human Molecular Genetics, 20(11), 2273-2284. [ddr092]. https://doi.org/10.1093/hmg/ddr092

Association of genetic variation with systolic and diastolic blood pressure among african americans : The candidate gene association resource study. / Fox, Ervin R.; Young, J. Hunter; Li, Yali; Dreisbach, Albert W.; Keating, Brendan J.; Musani, Solomon K.; Liu, Kiang; Morrison, Alanna C.; Ganesh, Santhi; Kutlar, Abdullah; Ramachandran, Vasan S.; Polak, Josef F.; Fabsitz, Richard R.; Dries, Daniel L.; Farlow, Deborah N.; Redline, Susan; Adeyemo, Adebowale; Hirschorn, Joel N.; Sun, Yan V.; Wyatt, Sharon B.; Penman, Alan D.; Palmas, Walter; Rotter, Jerome I.; Townsend, Raymond R.; Doumatey, Ayo P.; Tayo, Bamidele O.; Mosley, Thomas H.; Lyon, Helen N.; Kang, Sun J.; Rotimi, Charles N.; Cooper, Richard S.; Franceschini, Nora; Curb, J. David; Martin, Lisa W.; Eaton, Charles B.; Kardia, Sharon L.R.; Taylor, Herman A.; Caulfield, Mark J.; Ehret, Georg B.; Johnson, Toby; Chakravarti, Aravinda; Zhu, Xiaofeng; Levy, Daniel.

In: Human Molecular Genetics, Vol. 20, No. 11, ddr092, 01.06.2011, p. 2273-2284.

Research output: Contribution to journalArticle

Fox, ER, Young, JH, Li, Y, Dreisbach, AW, Keating, BJ, Musani, SK, Liu, K, Morrison, AC, Ganesh, S, Kutlar, A, Ramachandran, VS, Polak, JF, Fabsitz, RR, Dries, DL, Farlow, DN, Redline, S, Adeyemo, A, Hirschorn, JN, Sun, YV, Wyatt, SB, Penman, AD, Palmas, W, Rotter, JI, Townsend, RR, Doumatey, AP, Tayo, BO, Mosley, TH, Lyon, HN, Kang, SJ, Rotimi, CN, Cooper, RS, Franceschini, N, Curb, JD, Martin, LW, Eaton, CB, Kardia, SLR, Taylor, HA, Caulfield, MJ, Ehret, GB, Johnson, T, Chakravarti, A, Zhu, X & Levy, D 2011, 'Association of genetic variation with systolic and diastolic blood pressure among african americans: The candidate gene association resource study', Human Molecular Genetics, vol. 20, no. 11, ddr092, pp. 2273-2284. https://doi.org/10.1093/hmg/ddr092
Fox, Ervin R. ; Young, J. Hunter ; Li, Yali ; Dreisbach, Albert W. ; Keating, Brendan J. ; Musani, Solomon K. ; Liu, Kiang ; Morrison, Alanna C. ; Ganesh, Santhi ; Kutlar, Abdullah ; Ramachandran, Vasan S. ; Polak, Josef F. ; Fabsitz, Richard R. ; Dries, Daniel L. ; Farlow, Deborah N. ; Redline, Susan ; Adeyemo, Adebowale ; Hirschorn, Joel N. ; Sun, Yan V. ; Wyatt, Sharon B. ; Penman, Alan D. ; Palmas, Walter ; Rotter, Jerome I. ; Townsend, Raymond R. ; Doumatey, Ayo P. ; Tayo, Bamidele O. ; Mosley, Thomas H. ; Lyon, Helen N. ; Kang, Sun J. ; Rotimi, Charles N. ; Cooper, Richard S. ; Franceschini, Nora ; Curb, J. David ; Martin, Lisa W. ; Eaton, Charles B. ; Kardia, Sharon L.R. ; Taylor, Herman A. ; Caulfield, Mark J. ; Ehret, Georg B. ; Johnson, Toby ; Chakravarti, Aravinda ; Zhu, Xiaofeng ; Levy, Daniel. / Association of genetic variation with systolic and diastolic blood pressure among african americans : The candidate gene association resource study. In: Human Molecular Genetics. 2011 ; Vol. 20, No. 11. pp. 2273-2284.
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abstract = "The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide singlenucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P = 3.6 ×10-8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P = 4.7 × 10-8). The top IBC association for SBP was rs2012318 (P = 6.4 × 10-6)) near SLC25A42 and for DBP was rs2523586 (P = 1.3 3 10-6) near HLA-B. None of the top variants replicated in additional AA (n 5 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P = 0.009; TBX3-TBX5, P = 0.03; and CSK-ULK3, P = 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. The Author 2011. Published by Oxford University Press.",
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T1 - Association of genetic variation with systolic and diastolic blood pressure among african americans

T2 - The candidate gene association resource study

AU - Fox, Ervin R.

AU - Young, J. Hunter

AU - Li, Yali

AU - Dreisbach, Albert W.

AU - Keating, Brendan J.

AU - Musani, Solomon K.

AU - Liu, Kiang

AU - Morrison, Alanna C.

AU - Ganesh, Santhi

AU - Kutlar, Abdullah

AU - Ramachandran, Vasan S.

AU - Polak, Josef F.

AU - Fabsitz, Richard R.

AU - Dries, Daniel L.

AU - Farlow, Deborah N.

AU - Redline, Susan

AU - Adeyemo, Adebowale

AU - Hirschorn, Joel N.

AU - Sun, Yan V.

AU - Wyatt, Sharon B.

AU - Penman, Alan D.

AU - Palmas, Walter

AU - Rotter, Jerome I.

AU - Townsend, Raymond R.

AU - Doumatey, Ayo P.

AU - Tayo, Bamidele O.

AU - Mosley, Thomas H.

AU - Lyon, Helen N.

AU - Kang, Sun J.

AU - Rotimi, Charles N.

AU - Cooper, Richard S.

AU - Franceschini, Nora

AU - Curb, J. David

AU - Martin, Lisa W.

AU - Eaton, Charles B.

AU - Kardia, Sharon L.R.

AU - Taylor, Herman A.

AU - Caulfield, Mark J.

AU - Ehret, Georg B.

AU - Johnson, Toby

AU - Chakravarti, Aravinda

AU - Zhu, Xiaofeng

AU - Levy, Daniel

PY - 2011/6/1

Y1 - 2011/6/1

N2 - The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide singlenucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P = 3.6 ×10-8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P = 4.7 × 10-8). The top IBC association for SBP was rs2012318 (P = 6.4 × 10-6)) near SLC25A42 and for DBP was rs2523586 (P = 1.3 3 10-6) near HLA-B. None of the top variants replicated in additional AA (n 5 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P = 0.009; TBX3-TBX5, P = 0.03; and CSK-ULK3, P = 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. The Author 2011. Published by Oxford University Press.

AB - The prevalence of hypertension in African Americans (AAs) is higher than in other US groups; yet, few have performed genome-wide association studies (GWASs) in AA. Among people of European descent, GWASs have identified genetic variants at 13 loci that are associated with blood pressure. It is unknown if these variants confer susceptibility in people of African ancestry. Here, we examined genome-wide and candidate gene associations with systolic blood pressure (SBP) and diastolic blood pressure (DBP) using the Candidate Gene Association Resource (CARe) consortium consisting of 8591 AAs. Genotypes included genome-wide singlenucleotide polymorphism (SNP) data utilizing the Affymetrix 6.0 array with imputation to 2.5 million HapMap SNPs and candidate gene SNP data utilizing a 50K cardiovascular gene-centric array (ITMAT-Broad-CARe [IBC] array). For Affymetrix data, the strongest signal for DBP was rs10474346 (P = 3.6 ×10-8) located near GPR98 and ARRDC3. For SBP, the strongest signal was rs2258119 in C21orf91 (P = 4.7 × 10-8). The top IBC association for SBP was rs2012318 (P = 6.4 × 10-6)) near SLC25A42 and for DBP was rs2523586 (P = 1.3 3 10-6) near HLA-B. None of the top variants replicated in additional AA (n 5 11 882) or European-American (n = 69 899) cohorts. We replicated previously reported European-American blood pressure SNPs in our AA samples (SH2B3, P = 0.009; TBX3-TBX5, P = 0.03; and CSK-ULK3, P = 0.0004). These genetic loci represent the best evidence of genetic influences on SBP and DBP in AAs to date. More broadly, this work supports that notion that blood pressure among AAs is a trait with genetic underpinnings but also with significant complexity. The Author 2011. Published by Oxford University Press.

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