Rheumatoid arthritis: GWAS or TMI?

The risk of developing rheumatoid arthritis (RA), a common autoimmune disease characterized by inflammation and destruction of the joints, has long been known to be at least partially attributable to genetics. Recently, Gregersen and colleagues [1] reported that a common single nucleotide polymorphism (SNP) in the transcriptional regulatory gene REL confers a 1.2-fold greater risk of RA, on the basis of a solid and extensive investigation of a genome-wide association study (GWAS) in a large cohort of patients. Increased risk of similar magnitude has also been associated with SNPs in several other genes. Clearly the genetic basis of RA is complex, and polymorphisms in various genes have been associated with a greater risk of developing RA or of greater severity of the disease once an individual has RA.The techniques of GWAS can now be applied to a wider and wider range of diseases, thanks to technological advances in identifying genetic polymorphisms in large groups of individuals, advances in genotyping (for example, Gregersen et al. [1] included only RA patients expressing antibodies to citrullinated peptides), stronger collaborations among investigators at multiple institutions, and the availability of more sophisticated statistical and computational approaches to analyzing extremely large datasets. The studies described by Gregersen and colleagues [1] certainly exemplify a collaborative approach backed up by considerable technology and advanced data analysis. Investigators at 12 different academic institutions and one company in three different countries are listed as coauthors on the work, and state-of-the-art technology was used to analyze the frequency of 278,502 SNPs in 2,418 North American patients and 4,504 North American controls of European origin. The total number of patients was divided into discovery and replication cohorts to add rigor to the analysis, and the statistical analysis of the results was highly stringent and used standard computerized appr