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Genome-Wide association study of coronary heart disease and its risk factors in 8,090 african americans: The nhlbi CARe project

Lettre, G and Palmer, CD and Young, T and Ejebe, KG and Allayee, H and Benjamin, EJ and Bennett, F and Bowden, DW and Chakravarti, A and Dreisbach, A and Farlow, DN and Folsom, AR and Fornage, M and Forrester, T and Fox, E and Haiman, CA and Hartiala, J and Harris, TB and Hazen, SL and Heckbert, SR and Henderson, BE and Hirschhorn, JN and Keating, BJ and Kritchevsky, SB and Larkin, E and Li, M and Rudock, ME and McKenzie, CA and Meigs, JB and Meng, YA and Mosley, TH and Newman, AB and Newton-Cheh, CH and Paltoo, DN and Papanicolaou, GJ and Patterson, N and Post, WS and Psaty, BM and Qasim, AN and Qu, L and Rader, DJ and Redline, S and Reilly, MP and Reiner, AP and Rich, SS and Rotter, JI and Liu, Y and Shrader, P and Siscovick, DS and Tang, WHW and Taylor, HA and Tracy, RP and Vasan, RS and Waters, KM and Wilks, R and Wilson, JG and Fabsitz, RR and Gabriel, SB and Kathiresan, S and Boerwinkle, E (2011) Genome-Wide association study of coronary heart disease and its risk factors in 8,090 african americans: The nhlbi CARe project. PLoS Genetics, 7 (2). ISSN 1553-7390

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Abstract

Coronary heart disease (CHD) is the leading cause of mortality in African Americans. To identify common genetic polymorphisms associated with CHD and its risk factors (LDL- and HDL-cholesterol (LDL-C and HDL-C), hypertension, smoking, and type-2 diabetes) in individuals of African ancestry, we performed a genome-wide association study (GWAS) in 8,090 African Americans from five population-based cohorts. We replicated 17 loci previously associated with CHD or its risk factors in Caucasians. For five of these regions (CHD: CDKN2A/CDKN2B; HDL-C: FADS1-3, PLTP, LPL, and ABCA1), we could leverage the distinct linkage disequilibrium (LD) patterns in African Americans to identify DNA polymorphisms more strongly associated with the phenotypes than the previously reported index SNPs found in Caucasian populations. We also developed a new approach for association testing in admixed populations that uses allelic and local ancestry variation. Using this method, we discovered several loci that would have been missed using the basic allelic and global ancestry information only. Our conclusions suggest that no major loci uniquely explain the high prevalence of CHD in African Americans. Our project has developed resources and methods that address both admixture- and SNP-association to maximize power for genetic discovery in even larger African-American consortia.


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Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lettre, G
Palmer, CD
Young, T
Ejebe, KG
Allayee, H
Benjamin, EJ
Bennett, F
Bowden, DW
Chakravarti, A
Dreisbach, A
Farlow, DN
Folsom, AR
Fornage, M
Forrester, T
Fox, E
Haiman, CA
Hartiala, J
Harris, TB
Hazen, SL
Heckbert, SR
Henderson, BE
Hirschhorn, JN
Keating, BJ
Kritchevsky, SB
Larkin, E
Li, M
Rudock, ME
McKenzie, CA
Meigs, JB
Meng, YA
Mosley, TH
Newman, ABANEWMAN@pitt.eduANEWMAN
Newton-Cheh, CH
Paltoo, DN
Papanicolaou, GJ
Patterson, N
Post, WS
Psaty, BM
Qasim, AN
Qu, L
Rader, DJ
Redline, S
Reilly, MP
Reiner, AP
Rich, SS
Rotter, JI
Liu, Y
Shrader, P
Siscovick, DS
Tang, WHW
Taylor, HA
Tracy, RP
Vasan, RS
Waters, KM
Wilks, R
Wilson, JG
Fabsitz, RR
Gabriel, SB
Kathiresan, S
Boerwinkle, E
Date: 1 February 2011
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 7
Number: 2
DOI or Unique Handle: 10.1371/journal.pgen.1001300
Schools and Programs: Graduate School of Public Health > Epidemiology
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: African Americans--genetics; Cholesterol, HDL--genetics; Cholesterol, LDL--genetics; Coronary Disease--genetics; European Continental Ancestry Group; Genome, Human; Genome-Wide Association Study; Humans; Hypertension--genetics; Polymorphism, Single Nucleotide--genetics; Risk Factors; United States
Other ID: NLM PMC3037413
PubMed Central ID: PMC3037413
PubMed ID: 21347282
Date Deposited: 07 Aug 2012 15:46
Last Modified: 22 May 2019 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/13351

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