Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

Int Consortium Blood Pressure Geno; Jan Staessen

doi:10.1093/hmg/ddr092

Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study

Int Consortium Blood Pressure Geno, Jan Staessen

Research output: Contribution to journal › Article › Academic › peer-review

121 Citations (Web of Science)

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 single-nucleotide 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 ? 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 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.

Original language	English
Pages (from-to)	2273-2284
Journal	Human Molecular Genetics
Volume	20
Issue number	11
DOIs	https://doi.org/10.1093/hmg/ddr092
Publication status	Published - 1 Jun 2011

Access to Document

10.1093/hmg/ddr092

Cite this

@article{12113b0114864e249c968a2013e6cc88,

title = "Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study",

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 single-nucleotide 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 ? 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 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.",

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

year = "2011",

month = jun,

day = "1",

doi = "10.1093/hmg/ddr092",

language = "English",

volume = "20",

pages = "2273--2284",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "11",

}

TY - JOUR

T1 - Association of genetic variation with systolic and diastolic blood pressure among African Americans: 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., Jr.

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., Jr.

AU - Caulfield, Mark J.

AU - Ehret, Georg B.

AU - Johnson, Toby

AU - Chakravarti, Aravinda

AU - Zhu, Xiaofeng

AU - Int Consortium Blood Pressure Geno

AU - Staessen, Jan

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 single-nucleotide 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 ? 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 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.

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 single-nucleotide 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 ? 10(-6)) near HLA-B. None of the top variants replicated in additional AA (n = 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.

U2 - 10.1093/hmg/ddr092

DO - 10.1093/hmg/ddr092

M3 - Article

C2 - 21378095

SN - 0964-6906

VL - 20

SP - 2273

EP - 2284

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 11

ER -