title: C-reactive protein (CRP) promoter polymorphisms influence circulating CRP levels in a genome-wide association study of African Americans.
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 × 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.
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. doumateya@mail.nih.gov
authors.forename: Ayo P
authors.initials: AP
authors.lastname: Doumatey
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.forename: Fasil
authors.initials: F
authors.lastname: Tekola Ayele
authors.forename: Jie
authors.initials: J
authors.lastname: Zhou
authors.forename: Michael
authors.initials: M
authors.lastname: Erdos
authors.forename: Daniel
authors.initials: D
authors.lastname: Shriner
authors.forename: Hanxia
authors.initials: H
authors.lastname: Huang
authors.forename: Jokotade
authors.initials: J
authors.lastname: Adeleye
authors.forename: Williams
authors.initials: W
authors.lastname: Balogun
authors.forename: Olufemi
authors.initials: O
authors.lastname: Fasanmade
authors.forename: Thomas
authors.initials: T
authors.lastname: Johnson
authors.forename: Johnnie
authors.initials: J
authors.lastname: Oli
authors.forename: Godfrey
authors.initials: G
authors.lastname: Okafor
authors.forename: Albert
authors.initials: A
authors.lastname: Amoah
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Eghan
authors.forename: Kofi
authors.initials: K
authors.lastname: Agyenim-Boateng
authors.forename: Joseph
authors.initials: J
authors.lastname: Acheampong
authors.forename: Clement
authors.initials: C
authors.lastname: Adebamowo
authors.forename: Norman P
authors.initials: NP
authors.lastname: Gerry
authors.forename: Michael F
authors.initials: MF
authors.lastname: Christman
authors.forename: Adebowale
authors.initials: A
authors.lastname: Adeyemo
authors.forename: Charles N
authors.initials: CN
authors.lastname: Rotimi
mesh_terms: D001741:Black or African American / Q000235:genetics*; D002097:C-Reactive Protein / Q000032:analysis* / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D060148:HapMap Project; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D044465:White People / Q000235:genetics
chemical_list: D002097:C-Reactive Protein