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. Wyatt; Alan 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

doi:10.1093/hmg/ddr092

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

^*Corresponding author for this work

Preventive Medicine

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

147 Scopus citations

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 language	English (US)
Article number	ddr092
Pages (from-to)	2273-2284
Number of pages	12
Journal	Human molecular genetics
Volume	20
Issue number	11
DOIs	https://doi.org/10.1093/hmg/ddr092
State	Published - Jun 2011

Funding

The CARe authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The following nine parent studies have contributed parent study data, ancillary study data and DNA samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community. Atherosclerotic Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017), University of North Carolina, Forsyth County (N01-HC-55018); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study (CFS): Case Western Reserve University (RO1 HL46380-01-16); Cooperative Study of Sickle Cell Disease (CSSCD): University of Illinois (N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children’s Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc. (N01-HB-73003), Children’s Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St Luke’s Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St Jude’s Children’s Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195); Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), Harbor-UCLA Research and Education Institute (N01-HC-95169); Sleep Heart Health Study (SHHS): Johns Hopkins University (U01 HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocating in 2006 to University Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins University (U01 HL053937). The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100–32102, 32105, 32106, 32108, 32109, 32111–32113, 32115, 32118, 32119, 32122, 42107–42126, 42129–42132, and 44221. Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from National Heart, Lung, Blood Institute, and MD002249 from National Institute on Minority Health and Health Disparities. M.J.C. and T.J.’s contribution was facilitated by National Institute for Health Research support of the Barts and The London Cardiovascular Biomedical Research Unit. A.C. and a portion of the genotyping supported by HL086694 from National Heart, Lung, Blood Institute. Maywood African-American study are supported by the National Institutes of Health, grant number HL074166 from the National Heart, Lung, Blood Institute. Y.L. and X.Z. are supported by HL086718 from National Heart, Lung, Blood Institute and HG003054 from the National Human Genome Research Institute. The Howard University Family Study (HUFS) was supported by NIGMS/MBRS/SCORE grants to C.N.R. and A.A. with additional support from the Coriell Institute for Biomedical Sciences and the Intramural Research Program in the Center for Research in Genomics and Global Health, NHGRI/NIH (Z01HG200362). The ICBP-GWAS consortium was supported by many funding bodies including NIH/NHLBI, European and private funding agencies. Many of the participating studies and authors in ICBP-GWAS are members of the CHARGE and Global BPgen consortia. Details are provided in ref. 11. Funding to pay the Open Access publication charges for this article was provided by Herman Taylor, University of Mississippi Medical Center.

ASJC Scopus subject areas

Genetics(clinical)
Genetics
Molecular Biology

Access to Document

10.1093/hmg/ddr092

Cite this

Fox, E. R., Young, J. H., Li, Y., Dreisbach, A. W., Keating, B. J., Musani, S. K., Liu, K., Morrison, A. C., Ganesh, S., Kutlar, A., Ramachandran, V. S., Polak, J. F., Fabsitz, R. R., Dries, D. L., Farlow, D. N., Redline, S., Adeyemo, A., Hirschorn, J. N., Sun, Y. V., ... 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. Article ddr092. https://doi.org/10.1093/hmg/ddr092

@article{bd444627d7aa48e58324f9934b93cf45,

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 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.",

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.} 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.} and Caulfield, {Mark J.} and Ehret, {Georg B.} and Toby Johnson and Aravinda Chakravarti and Xiaofeng Zhu and Daniel Levy",

note = "Funding Information: The CARe authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The following nine parent studies have contributed parent study data, ancillary study data and DNA samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community. Atherosclerotic Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017), University of North Carolina, Forsyth County (N01-HC-55018); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study (CFS): Case Western Reserve University (RO1 HL46380-01-16); Cooperative Study of Sickle Cell Disease (CSSCD): University of Illinois (N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children{\textquoteright}s Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc. (N01-HB-73003), Children{\textquoteright}s Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St Luke{\textquoteright}s Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St Jude{\textquoteright}s Children{\textquoteright}s Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195); Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), Harbor-UCLA Research and Education Institute (N01-HC-95169); Sleep Heart Health Study (SHHS): Johns Hopkins University (U01 HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocating in 2006 to University Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins University (U01 HL053937). The Women{\textquoteright}s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100–32102, 32105, 32106, 32108, 32109, 32111–32113, 32115, 32118, 32119, 32122, 42107–42126, 42129–42132, and 44221. Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from National Heart, Lung, Blood Institute, and MD002249 from National Institute on Minority Health and Health Disparities. M.J.C. and T.J.{\textquoteright}s contribution was facilitated by National Institute for Health Research support of the Barts and The London Cardiovascular Biomedical Research Unit. A.C. and a portion of the genotyping supported by HL086694 from National Heart, Lung, Blood Institute. Maywood African-American study are supported by the National Institutes of Health, grant number HL074166 from the National Heart, Lung, Blood Institute. Y.L. and X.Z. are supported by HL086718 from National Heart, Lung, Blood Institute and HG003054 from the National Human Genome Research Institute. The Howard University Family Study (HUFS) was supported by NIGMS/MBRS/SCORE grants to C.N.R. and A.A. with additional support from the Coriell Institute for Biomedical Sciences and the Intramural Research Program in the Center for Research in Genomics and Global Health, NHGRI/NIH (Z01HG200362). The ICBP-GWAS consortium was supported by many funding bodies including NIH/NHLBI, European and private funding agencies. Many of the participating studies and authors in ICBP-GWAS are members of the CHARGE and Global BPgen consortia. Details are provided in ref. 11. Funding to pay the Open Access publication charges for this article was provided by Herman Taylor, University of Mississippi Medical Center.",

year = "2011",

month = jun,

doi = "10.1093/hmg/ddr092",

language = "English (US)",

volume = "20",

pages = "2273--2284",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "11",

}

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

TY - JOUR

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

N1 - Funding Information: The CARe authors wish to acknowledge the support of the National Heart, Lung, and Blood Institute and the contributions of the research institutions, study investigators, field staff and study participants in creating this resource for biomedical research. The following nine parent studies have contributed parent study data, ancillary study data and DNA samples through the Broad Institute (N01-HC-65226) to create this genotype/phenotype database for wide dissemination to the biomedical research community. Atherosclerotic Risk in Communities (ARIC): University of North Carolina at Chapel Hill (N01-HC-55015), Baylor Medical College (N01-HC-55016), University of Mississippi Medical Center (N01-HC-55021), University of Minnesota (N01-HC-55019), Johns Hopkins University (N01-HC-55020), University of Texas, Houston (N01-HC-55017), University of North Carolina, Forsyth County (N01-HC-55018); Cardiovascular Health Study (CHS): University of Washington (N01-HC-85079), Wake Forest University (N01-HC-85080), Johns Hopkins University (N01-HC-85081), University of Pittsburgh (N01-HC-85082), University of California, Davis (N01-HC-85083), University of California, Irvine (N01-HC-85084), New England Medical Center (N01-HC-85085), University of Vermont (N01-HC-85086), Georgetown University (N01-HC-35129), Johns Hopkins University (N01 HC-15103), University of Wisconsin (N01-HC-75150), Geisinger Clinic (N01-HC-45133), University of Washington (N01 HC-55222, U01 HL080295); Cleveland Family Study (CFS): Case Western Reserve University (RO1 HL46380-01-16); Cooperative Study of Sickle Cell Disease (CSSCD): University of Illinois (N01-HB-72982, N01-HB-97062), Howard University (N01-HB-72991, N01-HB-97061), University of Miami (N01-HB-72992, N01-HB-97064), Duke University (N01-HB-72993), George Washington University (N01-HB-72994), University of Tennessee (N01-HB-72995, N01-HB-97070), Yale University (N01-HB-72996, N01-HB-97072), Children’s Hospital-Philadelphia (N01-HB-72997, N01-HB-97056), University of Chicago (N01-HB-72998, N01-HB-97053), Medical College of Georgia (N01-HB-73000, N01-HB-97060), Washington University (N01-HB-73001, N01-HB-97071), Jewish Hospital and Medical Center of Brooklyn (N01-HB-73002), Trustees of Health and Hospitals of the City of Boston, Inc. (N01-HB-73003), Children’s Hospital-Oakland (N01-HB-73004, N01-HB-97054), University of Mississippi (N01-HB-73005), St Luke’s Hospital-New York (N01-HB-73006), Alta Bates-Herrick Hospital (N01-HB-97051), Columbia University (N01-HB-97058), St Jude’s Children’s Research Hospital (N01-HB-97066), Research Foundation, State University of New York-Albany (N01-HB-97068, N01-HB-97069), New England Research Institute (N01-HB-97073), Interfaith Medical Center-Brooklyn (N01-HB-97085); Coronary Artery Risk in Young Adults (CARDIA): University of Alabama at Birmingham (N01-HC-48047), University of Minnesota (N01-HC-48048), Northwestern University (N01-HC-48049), Kaiser Foundation Research Institute (N01-HC-48050), University of Alabama at Birmingham (N01-HC-95095), Tufts-New England Medical Center (N01-HC-45204), Wake Forest University (N01-HC-45205), Harbor-UCLA Research and Education Institute (N01-HC-05187), University of California, Irvine (N01-HC-45134, N01-HC-95100); Framingham Heart Study (FHS): Boston University (N01-HC-25195); Jackson Heart Study (JHS): Jackson State University (N01-HC-95170), University of Mississippi (N01-HC-95171), Tougaloo College (N01-HC-95172); Multi-Ethnic Study of Atherosclerosis (MESA): University of Washington (N01-HC-95159), Regents of the University of California (N01-HC-95160), Columbia University (N01-HC-95161), Johns Hopkins University (N01-HC-95162), University of Minnesota (N01-HC-95163), Northwestern University (N01-HC-95164), Wake Forest University (N01-HC-95165), University of Vermont (N01-HC-95166), New England Medical Center (N01-HC-95167), Johns Hopkins University (N01-HC-95168), Harbor-UCLA Research and Education Institute (N01-HC-95169); Sleep Heart Health Study (SHHS): Johns Hopkins University (U01 HL064360), Case Western University (U01 HL063463), University of California, Davis (U01 HL053916), University of Arizona (U01 HL053938), University of Minnesota (relocating in 2006 to University Arizona) (U01 HL053934), University of Pittsburgh (U01 HL077813), Boston University (U01 HL053941), MedStar Research Institute (U01 HL063429), Johns Hopkins University (U01 HL053937). The Women’s Health Initiative (WHI) program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100–32102, 32105, 32106, 32108, 32109, 32111–32113, 32115, 32118, 32119, 32122, 42107–42126, 42129–42132, and 44221. Genetic Epidemiology Network of Arteriopathy (GENOA) study is supported by the National Institutes of Health, grant numbers HL087660 and HL100245 from National Heart, Lung, Blood Institute, and MD002249 from National Institute on Minority Health and Health Disparities. M.J.C. and T.J.’s contribution was facilitated by National Institute for Health Research support of the Barts and The London Cardiovascular Biomedical Research Unit. A.C. and a portion of the genotyping supported by HL086694 from National Heart, Lung, Blood Institute. Maywood African-American study are supported by the National Institutes of Health, grant number HL074166 from the National Heart, Lung, Blood Institute. Y.L. and X.Z. are supported by HL086718 from National Heart, Lung, Blood Institute and HG003054 from the National Human Genome Research Institute. The Howard University Family Study (HUFS) was supported by NIGMS/MBRS/SCORE grants to C.N.R. and A.A. with additional support from the Coriell Institute for Biomedical Sciences and the Intramural Research Program in the Center for Research in Genomics and Global Health, NHGRI/NIH (Z01HG200362). The ICBP-GWAS consortium was supported by many funding bodies including NIH/NHLBI, European and private funding agencies. Many of the participating studies and authors in ICBP-GWAS are members of the CHARGE and Global BPgen consortia. Details are provided in ref. 11. Funding to pay the Open Access publication charges for this article was provided by Herman Taylor, University of Mississippi Medical Center.

PY - 2011/6

Y1 - 2011/6

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.

UR - http://www.scopus.com/inward/record.url?scp=79956051525&partnerID=8YFLogxK

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U2 - 10.1093/hmg/ddr092

DO - 10.1093/hmg/ddr092

M3 - Article

C2 - 21378095

AN - SCOPUS:79956051525

SN - 0964-6906

VL - 20

SP - 2273

EP - 2284

JO - Human molecular genetics

JF - Human molecular genetics

IS - 11

M1 - ddr092

ER -

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

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