Prospective associations of coronary heart disease loci in African Americans using the MetaboChip

The PAGE study

Nora Franceschini, Yijuan Hu, Alex P. Reiner, Steven Buyske, Mike Nalls, Lisa R. Yanek, Yun Li, Lucia A. Hindorff, Shelley A. Cole, Barbara V. Howard, Jeanette M. Stafford, Cara L. Carty, Praveen Sethupathy, Lisa W. Martin, Dan Yu Lin, Karen Johnson, Lewis C. Becker, Kari E. North, Abbas Dehghan, Joshua C. Bis & 11 others Yongmei Liu, Philip Greenland, Jo Ann E. Manson, Nobuyo Maeda, Melissa Garcia, Tamara B. Harris, Diane M. Becker, Christopher O'Donnell, Gerardo Heiss, Charles Kooperberg, Eric Boerwinkle

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans. Methods and Results: Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P=8.1×10-8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium. Conclusions: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.

Original languageEnglish (US)
Article numbere113203
JournalPloS one
Volume9
Issue number12
DOIs
StatePublished - Dec 26 2014

Fingerprint

African Americans
Coronary Disease
loci
women's health
ancestry
Women's Health
meta-analysis
Single Nucleotide Polymorphism
Meta-Analysis
coronary disease
atherosclerosis
cohort studies
Proportional Hazards Models
Gene Frequency
gene frequency
morbidity
Atherosclerosis
Hazards
Cohort Studies
Morbidity

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Franceschini, N., Hu, Y., Reiner, A. P., Buyske, S., Nalls, M., Yanek, L. R., ... Boerwinkle, E. (2014). Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: The PAGE study. PloS one, 9(12), [e113203]. https://doi.org/10.1371/journal.pone.0113203

Prospective associations of coronary heart disease loci in African Americans using the MetaboChip : The PAGE study. / Franceschini, Nora; Hu, Yijuan; Reiner, Alex P.; Buyske, Steven; Nalls, Mike; Yanek, Lisa R.; Li, Yun; Hindorff, Lucia A.; Cole, Shelley A.; Howard, Barbara V.; Stafford, Jeanette M.; Carty, Cara L.; Sethupathy, Praveen; Martin, Lisa W.; Lin, Dan Yu; Johnson, Karen; Becker, Lewis C.; North, Kari E.; Dehghan, Abbas; Bis, Joshua C.; Liu, Yongmei; Greenland, Philip; Manson, Jo Ann E.; Maeda, Nobuyo; Garcia, Melissa; Harris, Tamara B.; Becker, Diane M.; O'Donnell, Christopher; Heiss, Gerardo; Kooperberg, Charles; Boerwinkle, Eric.

In: PloS one, Vol. 9, No. 12, e113203, 26.12.2014.

Research output: Contribution to journalArticle

Franceschini, N, Hu, Y, Reiner, AP, Buyske, S, Nalls, M, Yanek, LR, Li, Y, Hindorff, LA, Cole, SA, Howard, BV, Stafford, JM, Carty, CL, Sethupathy, P, Martin, LW, Lin, DY, Johnson, K, Becker, LC, North, KE, Dehghan, A, Bis, JC, Liu, Y, Greenland, P, Manson, JAE, Maeda, N, Garcia, M, Harris, TB, Becker, DM, O'Donnell, C, Heiss, G, Kooperberg, C & Boerwinkle, E 2014, 'Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: The PAGE study', PloS one, vol. 9, no. 12, e113203. https://doi.org/10.1371/journal.pone.0113203
Franceschini, Nora ; Hu, Yijuan ; Reiner, Alex P. ; Buyske, Steven ; Nalls, Mike ; Yanek, Lisa R. ; Li, Yun ; Hindorff, Lucia A. ; Cole, Shelley A. ; Howard, Barbara V. ; Stafford, Jeanette M. ; Carty, Cara L. ; Sethupathy, Praveen ; Martin, Lisa W. ; Lin, Dan Yu ; Johnson, Karen ; Becker, Lewis C. ; North, Kari E. ; Dehghan, Abbas ; Bis, Joshua C. ; Liu, Yongmei ; Greenland, Philip ; Manson, Jo Ann E. ; Maeda, Nobuyo ; Garcia, Melissa ; Harris, Tamara B. ; Becker, Diane M. ; O'Donnell, Christopher ; Heiss, Gerardo ; Kooperberg, Charles ; Boerwinkle, Eric. / Prospective associations of coronary heart disease loci in African Americans using the MetaboChip : The PAGE study. In: PloS one. 2014 ; Vol. 9, No. 12.
@article{c6048c4b6d1240aeaf3701c5a4e4e636,
title = "Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: The PAGE study",
abstract = "Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans. Methods and Results: Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P=8.1×10-8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium. Conclusions: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.",
author = "Nora Franceschini and Yijuan Hu and Reiner, {Alex P.} and Steven Buyske and Mike Nalls and Yanek, {Lisa R.} and Yun Li and Hindorff, {Lucia A.} and Cole, {Shelley A.} and Howard, {Barbara V.} and Stafford, {Jeanette M.} and Carty, {Cara L.} and Praveen Sethupathy and Martin, {Lisa W.} and Lin, {Dan Yu} and Karen Johnson and Becker, {Lewis C.} and North, {Kari E.} and Abbas Dehghan and Bis, {Joshua C.} and Yongmei Liu and Philip Greenland and Manson, {Jo Ann E.} and Nobuyo Maeda and Melissa Garcia and Harris, {Tamara B.} and Becker, {Diane M.} and Christopher O'Donnell and Gerardo Heiss and Charles Kooperberg and Eric Boerwinkle",
year = "2014",
month = "12",
day = "26",
doi = "10.1371/journal.pone.0113203",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

TY - JOUR

T1 - Prospective associations of coronary heart disease loci in African Americans using the MetaboChip

T2 - The PAGE study

AU - Franceschini, Nora

AU - Hu, Yijuan

AU - Reiner, Alex P.

AU - Buyske, Steven

AU - Nalls, Mike

AU - Yanek, Lisa R.

AU - Li, Yun

AU - Hindorff, Lucia A.

AU - Cole, Shelley A.

AU - Howard, Barbara V.

AU - Stafford, Jeanette M.

AU - Carty, Cara L.

AU - Sethupathy, Praveen

AU - Martin, Lisa W.

AU - Lin, Dan Yu

AU - Johnson, Karen

AU - Becker, Lewis C.

AU - North, Kari E.

AU - Dehghan, Abbas

AU - Bis, Joshua C.

AU - Liu, Yongmei

AU - Greenland, Philip

AU - Manson, Jo Ann E.

AU - Maeda, Nobuyo

AU - Garcia, Melissa

AU - Harris, Tamara B.

AU - Becker, Diane M.

AU - O'Donnell, Christopher

AU - Heiss, Gerardo

AU - Kooperberg, Charles

AU - Boerwinkle, Eric

PY - 2014/12/26

Y1 - 2014/12/26

N2 - Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans. Methods and Results: Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P=8.1×10-8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium. Conclusions: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.

AB - Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality in African Americans. However, there is a paucity of studies assessing genetic determinants of CHD in African Americans. We examined the association of published variants in CHD loci with incident CHD, attempted to fine map these loci, and characterize novel variants influencing CHD risk in African Americans. Methods and Results: Up to 8,201 African Americans (including 546 first CHD events) were genotyped using the MetaboChip array in the Atherosclerosis Risk in Communities (ARIC) study and Women's Health Initiative (WHI). We tested associations using Cox proportional hazard models in sex- and study-stratified analyses and combined results using meta-analysis. Among 44 validated CHD loci available in the array, we replicated and fine-mapped the SORT1 locus, and showed same direction of effects as reported in studies of individuals of European ancestry for SNPs in 22 additional published loci. We also identified a SNP achieving array wide significance (MYC: rs2070583, allele frequency 0.02, P=8.1×10-8), but the association did not replicate in an additional 8,059 African Americans (577 events) from the WHI, HealthABC and GeneSTAR studies, and in a meta-analysis of 5 cohort studies of European ancestry (24,024 individuals including 1,570 cases of MI and 2,406 cases of CHD) from the CHARGE Consortium. Conclusions: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD in African Americans.

UR - http://www.scopus.com/inward/record.url?scp=84919935508&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84919935508&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0113203

DO - 10.1371/journal.pone.0113203

M3 - Article

VL - 9

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 12

M1 - e113203

ER -