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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/7783

Title: C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans
Authors: Doumatey, Ayo P.
Chen, Guanjie
Ayele, Fasil Tekola
Zhou, Jie
Erdos, Michael
Shriner, Daniel
Huang, Hanxia
Adeleye, Jokotade
Balogun, Williams
Fasanmade, Olufemi
Johnson, Thomas
Oli, Johnnie
Okafor, Godfrey
Amoah, Albert
Eghan, Benjamin A.
Agyenim-Boateng, Kofi
Acheampong, Joseph
Adebamowo, Clement
Gerry, Norman P.
Christman, Michael F.
Adeyemo, Adebowale
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
URI: http://hdl.handle.net/123456789/7783
Appears in Collections:College of Health Sciences

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