T1D and RA, making use of cases of one disease as controls for the other can reduce power to detect disease variants, a “dilution” of the genetic effect due to bias in the control group. The inclusion of disease samples in an expanded control group on a genome-wide basis can increase the false-positive error rate, since we may detect associations of large effect with these additional diseases, but may also unexpectedly result in an increase in power for variants influencing traits in opposite directions. However, these issues can be overcome by careful selection of appropriate diseases for expanding the control group and exclusion of SNPs known to be associated with these diseases.
