Zhuang and Morris [2009] compared a standard test of association between RA and genotype, using an additive genetic model and adjusting for covariates, to a sex-differentiated test [Kraft et al., 2007], and to a test of interaction with sex using a logistic regression framework. They found that signals of association in the major histocompatibility complex (MHC), which are now well established for RA, demonstrated strong effects in both sexes. However, they also identified eight novel SNPs that demonstrated genetic effects in only one sex, or reciprocal effects on risk in males and females. These SNPs were not significant in the standard main effect test of association that ignores possible heterogeneity of effect between sexes.
