Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.
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 perfo...
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Public Library of Science (PLoS)
2011
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oai:doaj.org-article:d9f44e2061144ffba888d0850b646b152021-11-18T06:17:44ZGenome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.1553-73901553-740410.1371/journal.pgen.1001300https://doaj.org/article/d9f44e2061144ffba888d0850b646b152011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347282/?tool=EBIhttps://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Coronary 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.Guillaume LettreCameron D PalmerTaylor YoungKenechi G EjebeHooman AllayeeEmelia J BenjaminFranklyn BennettDonald W BowdenAravinda ChakravartiAl DreisbachDeborah N FarlowAaron R FolsomMyriam FornageTerrence ForresterErvin FoxChristopher A HaimanJaana HartialaTamara B HarrisStanley L HazenSusan R HeckbertBrian E HendersonJoel N HirschhornBrendan J KeatingStephen B KritchevskyEmma LarkinMingyao LiMegan E RudockColin A McKenzieJames B MeigsYang A MengTom H MosleyAnne B NewmanChristopher H Newton-ChehDina N PaltooGeorge J PapanicolaouNick PattersonWendy S PostBruce M PsatyAtif N QasimLiming QuDaniel J RaderSusan RedlineMuredach P ReillyAlexander P ReinerStephen S RichJerome I RotterYongmei LiuPeter ShraderDavid S SiscovickW H Wilson TangHerman A TaylorRussell P TracyRamachandran S VasanKevin M WatersRainford WilksJames G WilsonRichard R FabsitzStacey B GabrielSekar KathiresanEric BoerwinklePublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 7, Iss 2, p e1001300 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Genetics QH426-470 |
| spellingShingle |
Genetics QH426-470 Guillaume Lettre Cameron D Palmer Taylor Young Kenechi G Ejebe Hooman Allayee Emelia J Benjamin Franklyn Bennett Donald W Bowden Aravinda Chakravarti Al Dreisbach Deborah N Farlow Aaron R Folsom Myriam Fornage Terrence Forrester Ervin Fox Christopher A Haiman Jaana Hartiala Tamara B Harris Stanley L Hazen Susan R Heckbert Brian E Henderson Joel N Hirschhorn Brendan J Keating Stephen B Kritchevsky Emma Larkin Mingyao Li Megan E Rudock Colin A McKenzie James B Meigs Yang A Meng Tom H Mosley Anne B Newman Christopher H Newton-Cheh Dina N Paltoo George J Papanicolaou Nick Patterson Wendy S Post Bruce M Psaty Atif N Qasim Liming Qu Daniel J Rader Susan Redline Muredach P Reilly Alexander P Reiner Stephen S Rich Jerome I Rotter Yongmei Liu Peter Shrader David S Siscovick W H Wilson Tang Herman A Taylor Russell P Tracy Ramachandran S Vasan Kevin M Waters Rainford Wilks James G Wilson Richard R Fabsitz Stacey B Gabriel Sekar Kathiresan Eric Boerwinkle Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. |
| description |
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. |
| format |
article |
| author |
Guillaume Lettre Cameron D Palmer Taylor Young Kenechi G Ejebe Hooman Allayee Emelia J Benjamin Franklyn Bennett Donald W Bowden Aravinda Chakravarti Al Dreisbach Deborah N Farlow Aaron R Folsom Myriam Fornage Terrence Forrester Ervin Fox Christopher A Haiman Jaana Hartiala Tamara B Harris Stanley L Hazen Susan R Heckbert Brian E Henderson Joel N Hirschhorn Brendan J Keating Stephen B Kritchevsky Emma Larkin Mingyao Li Megan E Rudock Colin A McKenzie James B Meigs Yang A Meng Tom H Mosley Anne B Newman Christopher H Newton-Cheh Dina N Paltoo George J Papanicolaou Nick Patterson Wendy S Post Bruce M Psaty Atif N Qasim Liming Qu Daniel J Rader Susan Redline Muredach P Reilly Alexander P Reiner Stephen S Rich Jerome I Rotter Yongmei Liu Peter Shrader David S Siscovick W H Wilson Tang Herman A Taylor Russell P Tracy Ramachandran S Vasan Kevin M Waters Rainford Wilks James G Wilson Richard R Fabsitz Stacey B Gabriel Sekar Kathiresan Eric Boerwinkle |
| author_facet |
Guillaume Lettre Cameron D Palmer Taylor Young Kenechi G Ejebe Hooman Allayee Emelia J Benjamin Franklyn Bennett Donald W Bowden Aravinda Chakravarti Al Dreisbach Deborah N Farlow Aaron R Folsom Myriam Fornage Terrence Forrester Ervin Fox Christopher A Haiman Jaana Hartiala Tamara B Harris Stanley L Hazen Susan R Heckbert Brian E Henderson Joel N Hirschhorn Brendan J Keating Stephen B Kritchevsky Emma Larkin Mingyao Li Megan E Rudock Colin A McKenzie James B Meigs Yang A Meng Tom H Mosley Anne B Newman Christopher H Newton-Cheh Dina N Paltoo George J Papanicolaou Nick Patterson Wendy S Post Bruce M Psaty Atif N Qasim Liming Qu Daniel J Rader Susan Redline Muredach P Reilly Alexander P Reiner Stephen S Rich Jerome I Rotter Yongmei Liu Peter Shrader David S Siscovick W H Wilson Tang Herman A Taylor Russell P Tracy Ramachandran S Vasan Kevin M Waters Rainford Wilks James G Wilson Richard R Fabsitz Stacey B Gabriel Sekar Kathiresan Eric Boerwinkle |
| author_sort |
Guillaume Lettre |
| title |
Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. |
| title_short |
Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. |
| title_full |
Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. |
| title_fullStr |
Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. |
| title_full_unstemmed |
Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. |
| title_sort |
genome-wide association study of coronary heart disease and its risk factors in 8,090 african americans: the nhlbi care project. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/d9f44e2061144ffba888d0850b646b15 |
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