C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans

dc.contributor.authorDoumatey, A.P.
dc.contributor.authorChen, G.
dc.contributor.authorAyele, F.T.
dc.contributor.authorZhou, J.
dc.contributor.authorErdos, M.
dc.contributor.authorShriner, D.
dc.contributor.authorHuang, H.
dc.contributor.authorAdeleye, J.
dc.contributor.authorBalogun, W.
dc.contributor.authorFasanmade, O.
dc.contributor.authorJohnson, T.
dc.contributor.authorOli, J.
dc.contributor.authorOkafor, G.
dc.contributor.authorAmoah, A.
dc.contributor.authorEghan, B.A.
dc.contributor.authorAgyenim-Boateng, K.
dc.contributor.authorAcheampong, J.
dc.contributor.authorAdebamowo, C.
dc.contributor.authorGerry, N.P.
dc.contributor.authorChristman, M.F.
dc.contributor.authorAdeyemo, A.
dc.contributor.authorRotimi, C.N.
dc.date.accessioned2013-06-26T21:26:46Z
dc.date.accessioned2017-10-19T11:57:31Z
dc.date.available2013-06-26T21:26:46Z
dc.date.available2017-10-19T11:57:31Z
dc.date.issued2012-07
dc.description.abstractC-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 × 10-8 and P < 0.05, respectively. Ten SNPs in (CRP pseudogene-1) CRPP1 and CRP genes were associated with serum CRP (P = 2.4 × 10-09 to 4.3 × 10-11). 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.en_US
dc.identifier.citationDoumatey, A. P., Chen, G., Amoah, A. G., Zhou, J., Erdos, M., Shriner, D., . . . Rotimi, C. N. (2012). C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans. Human Molecular Genetics, 21(13), 3063-3072en_US
dc.identifier.issn09646906
dc.identifier.urihttp://197.255.68.203/handle/123456789/4236
dc.language.isoenen_US
dc.publisherHuman Molecular Geneticsen_US
dc.subjectAfrican Americansen_US
dc.subjectC-Reactive Proteinen_US
dc.subjectEuropean Continental Ancestry Groupen_US
dc.subjectFemaleen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectGenotypeen_US
dc.subjectHapMap Projecten_US
dc.subjectHumansen_US
dc.subjectLinkage Disequilibriumen_US
dc.subjectMaleen_US
dc.subjectMiddle Ageden_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectPromoter Regions, Geneticen_US
dc.titleC-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americansen_US
dc.typeArticleen_US

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