The genotypes of three IRF5 SNPs, that form the previously identified SLE risk haplotype in the Mexican population, were used for gene–gene interaction analysis between IRF5 and TYK2. Epistasis analysis generated a three-way epistatic model between the TYK2 rs280500 polymorphism and the two IRF5 rs2004640 and rs2070197 polymorphisms (Table 4). Here, TYK2 is linked to systemic lupus erythematosus.