Research Articles >
College of Health Sciences >
Please use this identifier to cite or link to this item:
|Title: ||C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans|
|Authors: ||Doumatey, Ayo P.|
Ayele, Fasil Tekola
Eghan, Benjamin A.
Gerry, Norman P.
Christman, Michael F.
Rotimi, Charles N.
|Issue Date: ||2012|
|Publisher: ||Human Molecular Genetics|
|Citation: ||Human Molecular Genetics, 2012, Vol. 21, No. 13 3063–3072|
|Abstract: ||C-reactive protein (CRP) is an acute phase reactant protein produced primarily by the liver. Circulating CRP
levels are influenced by genetic and non-genetic factors, including infection and obesity. Genome-wide association
studies (GWAS) provide an unbiased approach towards identifying loci influencing CRP levels.
None of the six GWAS for CRP levels has been conducted in an African ancestry population. The present
study aims to: (i) identify genetic variants that influence serum CRP in African Americans (AA) using a
genome-wide association approach and replicate these findings in West Africans (WA), (ii) assess transferability
of major signals for CRP reported in European ancestry populations (EA) to AA and (iii) use the weak
linkage disequilibrium (LD) structure characteristic of African ancestry populations to fine-map the previously
reported CRP locus. The discovery cohort comprised 837 unrelated AA, with the replication of significant
single-nucleotide polymorphisms (SNPs) assessed in 486 WA. The association analysis was conducted with
2 366 856 genotyped and imputed SNPs under an additive genetic model with adjustment for appropriate covariates.
Genome-wide and replication significances were set at P < 5 3 1028 and P < 0.05, respectively. Ten
SNPs in (CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P 5 2.4 3 10209 to
4.3 3 10211). All but one of the top-scoring SNPs associated with CRP in AA were successfully replicated
in WA. CRP signals previously identified in EA samples were transferable to AAs, and we were able to
fine-map this signal, reducing the region of interest from the 25 kb of LD around the locus in the HapMap
CEU sample to only 8 kb in our AA sample.|
|Description: ||Human Molecular Genetics, 2012, Vol. 21, No. 13 3063–3072. Also available at doi:10.1093/hmg/dds133|
|Appears in Collections:||College of Health Sciences|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.