title: Investigation of Caucasian rheumatoid arthritis susceptibility loci in African patients with the same disease.
abstract: BACKGROUND
  The largest genetic risk to develop rheumatoid arthritis (RA) arises from a group of alleles of the HLA DRB1 locus ('shared epitope', SE). Over 30 non-HLA single nucleotide polymorphisms (SNPs) predisposing to disease have been identified in Caucasians, but they have never been investigated in West/Central Africa. We previously reported a lower prevalence of the SE in RA patients in Cameroon compared to European patients and aimed in the present study to investigate the contribution of Caucasian non-HLA RA SNPs to disease susceptibility in Black Africans.
  
  
  METHODS
  RA cases and controls from Cameroon were genotyped for Caucasian RA susceptibility SNPs using Sequenom MassArray technology. Genotype data were also available for 5024 UK cases and 4281 UK controls and for 119 Yoruba individuals in Ibadan, Nigeria (YRI, HapMap). A Caucasian aggregate genetic-risk score (GRS) was calculated as the sum of the weighted risk-allele counts.
  
  
  RESULTS
  After genotyping quality control procedures were performed, data on 28 Caucasian non-HLA susceptibility SNPs were available in 43 Cameroonian RA cases and 44 controls. The minor allele frequencies (MAF) were tightly correlated between Cameroonian controls and YRI individuals (correlation coefficient 93.8%, p = 1.7E-13), and they were pooled together. There was no correlation between MAF of UK and African controls; 13 markers differed by more than 20%. The MAF for markers at PTPN22, IL2RA, FCGR2A and IL2/IL21 was below 2% in Africans. The GRS showed a strong association with RA in the UK. However, the GRS did not predict RA in Africans (OR = 0.71, 95% CI 0.29 - 1.74, p = 0.456). Random sampling from the UK cohort showed that this difference in association is unlikely to be explained by small sample size or chance, but is statistically significant with p<0.001.
  
  
  CONCLUSIONS
  The MAFs of non-HLA Caucasian RA susceptibility SNPs are different between Caucasians and Africans, and several polymorphisms are barely detectable in West/Central Africa. The genetic risk of developing RA conferred by a set of 28 Caucasian susceptibility SNPs is significantly different between the UK and Africa with p<0.001. Taken together, these observations strengthen the hypothesis that the genetic architecture of RA susceptibility is different in different ethnic backgrounds.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Viatte
authors.forename: Edward
authors.initials: E
authors.lastname: Flynn
authors.forename: Mark
authors.initials: M
authors.lastname: Lunt
authors.forename: Joanne
authors.initials: J
authors.lastname: Barnes
authors.forename: Madeleine
authors.initials: M
authors.lastname: Singwe-Ngandeu
authors.forename: Sylvette
authors.initials: S
authors.lastname: Bas
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000208:ethnology / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D002163:Cameroon; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009549:Nigeria; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D006113:United Kingdom; D044465:White People / Q000235:genetics*
chemical_list: D059811:HLA-DRB1 Chains