Because of the limitations of candidate gene studies and linkage analyses for common diseases, genome-wide association studies are now recognized as a powerful approach to mapping responsible genes with modest effects on various diseases. We performed whole genome case-control linkage disequilibrium (LD) mapping for rheumatoid arthritis (RA)-associated genes in Japanese subjects using single nucleotide polymorphisms (SNPs) mainly discovered in gene-containing regions. We identified RA-associated polymorphisms in two genes/loci, PADI4 and SLC22A4/A5 cluster. PADI4 catalyzes the conversion of arginine residues to citrulline in proteins. Recent reports on the high specificity of autoantibodies against citrullinated proteins to RA and the results of our study suggest that citrullination by PADI4 is a fundamental phenomenon of RA. On the other hand, the functions of SLC22A4/A5 have not been studied in detail, but SLC22A4/A5 have been reported to have multiple polymorphisms associated with several autoimmune diseases. Thus, large-scale LD mapping appears to be effective for identifying RA-associated polymorphisms.