Prospective associations of coronary heart disease loci in African Americans using the MetaboChip: the PAGE study.

MedStar author(s):
Citation: PLoS ONE [Electronic Resource]. 9(12):e113203, 2014.PMID: 25542012Institution: MedStar Health Research InstituteForm of publication: Journal ArticleMedline article type(s): Journal Article | Meta-Analysis | Research Support, N.I.H., Extramural | Research Support, N.I.H., Intramural | Research Support, U.S. Gov't, P.H.S.Subject headings: *Adaptor Proteins, Vesicular Transport/ge [Genetics] | *African Americans/ge [Genetics] | *Coronary Disease/ge [Genetics] | *Proto-Oncogene Proteins c-myc/ge [Genetics] | Coronary Disease/eh [Ethnology] | Coronary Disease/ep [Epidemiology] | Female | Genetic Association Studies/mt [Methods] | Genetic Predisposition to Disease | Humans | Male | Oligonucleotide Array Sequence Analysis/mt [Methods] | Polymorphism, Single Nucleotide | Prospective StudiesLocal holdings: Available online through MWHC library: 2006 - presentISSN:
  • 1932-6203
Name of journal: PloS oneAbstract: 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.CONCLUSIONS: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD 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 x 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.All authors: Becker DM, Becker LC, Bis JC, Boerwinkle E, Buyske S, Carty CL, Cole SA, Dehghan A, Franceschini N, Garcia M, Greenland P, Harris TB, Heiss G, Hindorff LA, Howard BV, Hu Y, Johnson KC, Kooperberg C, Li Y, Lin DY, Liu Y, Maeda N, Manson JE, Martin LW, Nalls M, North KE, O'Donnell C, Reiner AP, Sethupathy P, Stafford JM, Yanek LRDigital Object Identifier: Date added to catalog: 2016-01-13
Holdings
Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article Available 25542012

Available online through MWHC library: 2006 - present

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.

CONCLUSIONS: Our findings suggest that some CHD loci previously identified in individuals of European ancestry may be relevant to incident CHD 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 x 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.

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