The failure of GWAS analysis of more than 9,000 cases of MD (Ripke et al., 2013b) to find robust evidence for loci that exceed genome-wide significance is compatible with a paradigm in which the majority of the genetic variance is due to the joint effect of multiple loci of small effect. Twin studies and SNP-based heritability tests of the samples used for genome-wide association discount the possibility that there are no genetic effects to be found, leaving two nonmutually exclusive possibilities: either the effects are smaller than expected and/or the disorder is heterogeneous: different diseases might manifest with similar symptoms (incorrectly identified as the same illness), or there may be many different pathways to the same outcome (different environmental precipitants trigger MD in different ways, according to the genetic susceptibility of the individual).
