The WTCCC present “expanded reference group analyses,” combining controls with all additional disease samples, increasing the reference group ratio from 1.5:1.0 for each disease to up to approximately 7.5:1.0. Such an analysis is mutually beneficial to all diseases represented in the multisample study. To allow for pleiotropic effects, only nonautoimmune diseases were used in the expanded reference groups for T1D, RA, and Crohn's disease (CD), and CAD and hypertension were not tested against each other. Application of these expanded reference group analyses resulted in more significant evidence of association at the most compelling loci identified in the primary analysis, as well as for established loci for T1D, T2D, and CD.
