Genome-wide admixture mapping for coronary artery calcification in African Americans

The NHLBI family heart study

Qunyuan Zhang, Cora E. Lewis, Lynne E. Wagenknecht, Richard H. Myers, James S. Pankow, Steven Hunt, Kari E. North, James E. Hixson, J. Jeffrey Carr, Lawrence C. Shimmin, Ingrid Borecki, Michael A. Province

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Coronary artery calcification (CAC) is an important measure of subclinical coronary atherosclerosis and an independent predictor of coronary heart disease. To identify the genetic loci contributing to CAC, we conducted a genome-wide scan with 374 microsatellite markers by applying admixture mapping to 618 African American participants in the US National Heart, Lung, and Blood Institute Family Heart Study, in which 868 European American participants from family heart study and 157 Africans genotyped by the Marshfield Medical Genetics Center were used as the two reference founding populations for the African Americans, and a computer program based on a Markov Chain Monte Carlo algorithm, STRUCTURE 2.1, was used to estimate European and African ancestries among African Americans. A permutation test for random repeated sampling regression of CAC score on marker specific African ancestry found 22 markers statistically significant at the 0.05 level and four markers, D10S189 at 10p14, D20S159 at 20q13, D12S1294 at 12q14, and D6S1053 at 6q12, significant at the 0.01 level. D10S189 and D6S1053 were further confirmed at the 0.05 significance level by regression of CAC on allelic copy number, in which individual ancestry was used as a genetic background covariate to control possible stratification in African Americans. On the basis of the results from this and other independent studies, the location of D6S1053 at 80cM on chromosome 6 (6q12) seems to harbor a highly promising quantitative trait loci for atherosclerosis.

Original languageEnglish
Pages (from-to)264-272
Number of pages9
JournalGenetic Epidemiology
Volume32
Issue number3
DOIs
Publication statusPublished - Apr 2008
Externally publishedYes

Fingerprint

National Heart, Lung, and Blood Institute (U.S.)
African Americans
Coronary Vessels
Genome
Markov Chains
Chromosomes, Human, Pair 6
Genetic Loci
Quantitative Trait Loci
Medical Genetics
Microsatellite Repeats
Coronary Disease
Coronary Artery Disease
Atherosclerosis
Software
Population

Keywords

  • Admixture mapping
  • African Americans
  • Atherosclerosis
  • Coronary artery calcification
  • Genome scan

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Zhang, Q., Lewis, C. E., Wagenknecht, L. E., Myers, R. H., Pankow, J. S., Hunt, S., ... Province, M. A. (2008). Genome-wide admixture mapping for coronary artery calcification in African Americans: The NHLBI family heart study. Genetic Epidemiology, 32(3), 264-272. https://doi.org/10.1002/gepi.20301

Genome-wide admixture mapping for coronary artery calcification in African Americans : The NHLBI family heart study. / Zhang, Qunyuan; Lewis, Cora E.; Wagenknecht, Lynne E.; Myers, Richard H.; Pankow, James S.; Hunt, Steven; North, Kari E.; Hixson, James E.; Carr, J. Jeffrey; Shimmin, Lawrence C.; Borecki, Ingrid; Province, Michael A.

In: Genetic Epidemiology, Vol. 32, No. 3, 04.2008, p. 264-272.

Research output: Contribution to journalArticle

Zhang, Q, Lewis, CE, Wagenknecht, LE, Myers, RH, Pankow, JS, Hunt, S, North, KE, Hixson, JE, Carr, JJ, Shimmin, LC, Borecki, I & Province, MA 2008, 'Genome-wide admixture mapping for coronary artery calcification in African Americans: The NHLBI family heart study', Genetic Epidemiology, vol. 32, no. 3, pp. 264-272. https://doi.org/10.1002/gepi.20301
Zhang, Qunyuan ; Lewis, Cora E. ; Wagenknecht, Lynne E. ; Myers, Richard H. ; Pankow, James S. ; Hunt, Steven ; North, Kari E. ; Hixson, James E. ; Carr, J. Jeffrey ; Shimmin, Lawrence C. ; Borecki, Ingrid ; Province, Michael A. / Genome-wide admixture mapping for coronary artery calcification in African Americans : The NHLBI family heart study. In: Genetic Epidemiology. 2008 ; Vol. 32, No. 3. pp. 264-272.
@article{4d435e30c3244dabbc9a47ff13b7c6bd,
title = "Genome-wide admixture mapping for coronary artery calcification in African Americans: The NHLBI family heart study",
abstract = "Coronary artery calcification (CAC) is an important measure of subclinical coronary atherosclerosis and an independent predictor of coronary heart disease. To identify the genetic loci contributing to CAC, we conducted a genome-wide scan with 374 microsatellite markers by applying admixture mapping to 618 African American participants in the US National Heart, Lung, and Blood Institute Family Heart Study, in which 868 European American participants from family heart study and 157 Africans genotyped by the Marshfield Medical Genetics Center were used as the two reference founding populations for the African Americans, and a computer program based on a Markov Chain Monte Carlo algorithm, STRUCTURE 2.1, was used to estimate European and African ancestries among African Americans. A permutation test for random repeated sampling regression of CAC score on marker specific African ancestry found 22 markers statistically significant at the 0.05 level and four markers, D10S189 at 10p14, D20S159 at 20q13, D12S1294 at 12q14, and D6S1053 at 6q12, significant at the 0.01 level. D10S189 and D6S1053 were further confirmed at the 0.05 significance level by regression of CAC on allelic copy number, in which individual ancestry was used as a genetic background covariate to control possible stratification in African Americans. On the basis of the results from this and other independent studies, the location of D6S1053 at 80cM on chromosome 6 (6q12) seems to harbor a highly promising quantitative trait loci for atherosclerosis.",
keywords = "Admixture mapping, African Americans, Atherosclerosis, Coronary artery calcification, Genome scan",
author = "Qunyuan Zhang and Lewis, {Cora E.} and Wagenknecht, {Lynne E.} and Myers, {Richard H.} and Pankow, {James S.} and Steven Hunt and North, {Kari E.} and Hixson, {James E.} and Carr, {J. Jeffrey} and Shimmin, {Lawrence C.} and Ingrid Borecki and Province, {Michael A.}",
year = "2008",
month = "4",
doi = "10.1002/gepi.20301",
language = "English",
volume = "32",
pages = "264--272",
journal = "Genetic Epidemiology",
issn = "0741-0395",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Genome-wide admixture mapping for coronary artery calcification in African Americans

T2 - The NHLBI family heart study

AU - Zhang, Qunyuan

AU - Lewis, Cora E.

AU - Wagenknecht, Lynne E.

AU - Myers, Richard H.

AU - Pankow, James S.

AU - Hunt, Steven

AU - North, Kari E.

AU - Hixson, James E.

AU - Carr, J. Jeffrey

AU - Shimmin, Lawrence C.

AU - Borecki, Ingrid

AU - Province, Michael A.

PY - 2008/4

Y1 - 2008/4

N2 - Coronary artery calcification (CAC) is an important measure of subclinical coronary atherosclerosis and an independent predictor of coronary heart disease. To identify the genetic loci contributing to CAC, we conducted a genome-wide scan with 374 microsatellite markers by applying admixture mapping to 618 African American participants in the US National Heart, Lung, and Blood Institute Family Heart Study, in which 868 European American participants from family heart study and 157 Africans genotyped by the Marshfield Medical Genetics Center were used as the two reference founding populations for the African Americans, and a computer program based on a Markov Chain Monte Carlo algorithm, STRUCTURE 2.1, was used to estimate European and African ancestries among African Americans. A permutation test for random repeated sampling regression of CAC score on marker specific African ancestry found 22 markers statistically significant at the 0.05 level and four markers, D10S189 at 10p14, D20S159 at 20q13, D12S1294 at 12q14, and D6S1053 at 6q12, significant at the 0.01 level. D10S189 and D6S1053 were further confirmed at the 0.05 significance level by regression of CAC on allelic copy number, in which individual ancestry was used as a genetic background covariate to control possible stratification in African Americans. On the basis of the results from this and other independent studies, the location of D6S1053 at 80cM on chromosome 6 (6q12) seems to harbor a highly promising quantitative trait loci for atherosclerosis.

AB - Coronary artery calcification (CAC) is an important measure of subclinical coronary atherosclerosis and an independent predictor of coronary heart disease. To identify the genetic loci contributing to CAC, we conducted a genome-wide scan with 374 microsatellite markers by applying admixture mapping to 618 African American participants in the US National Heart, Lung, and Blood Institute Family Heart Study, in which 868 European American participants from family heart study and 157 Africans genotyped by the Marshfield Medical Genetics Center were used as the two reference founding populations for the African Americans, and a computer program based on a Markov Chain Monte Carlo algorithm, STRUCTURE 2.1, was used to estimate European and African ancestries among African Americans. A permutation test for random repeated sampling regression of CAC score on marker specific African ancestry found 22 markers statistically significant at the 0.05 level and four markers, D10S189 at 10p14, D20S159 at 20q13, D12S1294 at 12q14, and D6S1053 at 6q12, significant at the 0.01 level. D10S189 and D6S1053 were further confirmed at the 0.05 significance level by regression of CAC on allelic copy number, in which individual ancestry was used as a genetic background covariate to control possible stratification in African Americans. On the basis of the results from this and other independent studies, the location of D6S1053 at 80cM on chromosome 6 (6q12) seems to harbor a highly promising quantitative trait loci for atherosclerosis.

KW - Admixture mapping

KW - African Americans

KW - Atherosclerosis

KW - Coronary artery calcification

KW - Genome scan

UR - http://www.scopus.com/inward/record.url?scp=42249087163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42249087163&partnerID=8YFLogxK

U2 - 10.1002/gepi.20301

DO - 10.1002/gepi.20301

M3 - Article

VL - 32

SP - 264

EP - 272

JO - Genetic Epidemiology

JF - Genetic Epidemiology

SN - 0741-0395

IS - 3

ER -