hits than would be expected by chance, i.e. the total sample with bipolar disorder is genetically heterogeneous. Under the alternative hypothesis, the subset under investigation is postulated to have properties that facilitate the detection of genetic effects. Such properties include a higher genetic loading or, perhaps more plausibly since bipolar disorder broadly defined has already a high heritability, a greater degree of genetic homogeneity for the subset. Although it may seem counter-intuitive that more homogeneity (i.e. fewer risk genes) would lead to the detection of greater numbers of risk genes, such a scenario is entirely expected. This is because the reduction in the number of risk loci in the subset compared with that in bipolar disorder as a whole would effectively increase the effect size at any one locus and thus the ease of detection.
