The data we have summarized so far are compatible with the hypothesis that the genetic basis of MD arises from the joint effect of very many loci of small effect, with odds ratios of much less than 1.2. However, it is also compatible with the existence of larger effect loci, under two alternative (but not incompatible) hypotheses; first, some of the heritability of MD is explained by rare relatively large-effect loci; second, larger effect sizes would be observed if more homogeneous heritable phenotypic groupings could be identified. We consider in this section whether rare, large-effect variants might exist and return to the issues of phenotypic homogeneity later.
