- Erratum in:
- Arthritis Rheum. 2008 Oct;58(10):3276.
Genome-wide association study of rheumatoid arthritis in the Spanish population: KLF12 as a risk locus for rheumatoid arthritis susceptibility.
Julià A,
Ballina J,
Cañete JD,
Balsa A,
Tornero-Molina J,
Naranjo A,
Alperi-López M,
Erra A,
Pascual-Salcedo D,
Barceló P,
Camps J,
Marsal S.
Institut de Recerca, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
OBJECTIVE: To identify new genes associated with susceptibility to rheumatoid arthritis (RA), using a 2-stage genome-wide association study. METHODS: Following a liability-based study design, we analyzed 317,503 single-nucleotide polymorphisms (SNPs) in 400 patients with RA and 400 control subjects. We selected a group of candidate SNPs for replication in an independent group of 410 patients with RA and 394 control subjects. Using data from the 3 previous genome-wide association studies in RA, we also looked for genomic regions showing evidence of common association signals. Finally, we analyzed the presence of genome-wide epistasis using the binary test implemented in the PLINK program. RESULTS: We identified several genomic regions showing evidence of genome-wide association (P < 1 x 10(-5)). In the replication analysis, we identified KLF12 SNP rs1324913 as the most strongly associated SNP (P = 0.01). In our study, we observed that this SNP showed higher significance than PTPN22 SNP rs2476601, in both the genome-wide association studies and the replication analyses. Furthermore, the integration of our data with those from previous genome-wide association studies showed that KLF12 and PTPRT are the unique loci that are commonly associated in 3 different studies (P = 0.004 and P = 0.002 for KLF12 in the Wellcome Trust Case Control Consortium study and the Brigham and Women's Rheumatoid Arthritis Sequential Study genome-wide association study, respectively). The genome-wide epistasis analysis identified several SNP pairs close to significance after multiple test correction. CONCLUSION: The present genome-wide association study identified KLF12 as a new susceptibility gene for RA. The joint analysis of our results and those from previous genome-wide association studies showed genomic regions with a higher probability of being genuine susceptibility loci for RA.
PMID: 18668548 [PubMed - indexed for MEDLINE]