Although rg is an informative measure of the genetic similarity between two phenotypes, it does not capture all dimensions of genetic overlap. Shared genetic variants can have either concordant or discordant effects.12,17,18 However, since rg is a genome-wide summary measure, it does not differentiate genetic overlap with a mixture of concordant and discordant effects from an absence of genetic overlap, returning an estimate close to 0 in both scenarios (fig. 1a). It is necessary to capture this “missing dimension” of genetic overlap to comprehensively describe the shared genetic underpinnings of polygenic mental disorders.17 Overlap despite minimal genetic correlation may indicate shared molecular mechanisms with implications for how we conceptualise genetic risk for mental disorders.
