First, we used univariate MiXeR to show that the genetic architectures of mental traits exhibit fundamental differences beyond heritability, with differences in polygenicity across the eight included traits. Among mental disorders, this was most pronounced between ADHD and MD, although lower polygenicities have recently been reported for migraine24, cortical MRI measures, and other somatic traits.24–26 While the neurobiological and clinical implications of these findings are currently speculative, it is possible that polygenicity is a marker of heterogeneity at the neurobiological and/or clinical level. For example, ADHD may represent a more neurobiologically and/or clinically homogenous population than MD. By extension, polygenicity may be a useful marker of genetic heterogeneity, which could be used to test the effect of biomarkers or clinically defined sub-groups on the genetic make-up of a given disorder. Differences in polygenicity may also be due to differences in biological complexity or negative selection.27,28 More deeply-phenotyped samples and improved functional characterisation of genetic loci are required to provide further insights.
