Genome-wide associations between single-nucleotide polymorphisms and clinical traits were simultaneously conducted using penalized orthogonal-components regression. This method was developed to identify the genetic variants controlling phenotypes from a massive number of candidate variants. By investigating the association between all single-nucleotide polymorphisms to the phenotype of antibodies against cyclic citrullinated peptide using the rheumatoid arthritis data provided by Genetic Analysis Workshop 16, we identified genetic regions which may contribute to the pathogenesis of rheumatoid arthritis. Bioinformatic analysis of these genomic regions showed most of them harbor protein-coding gene(s).