The PRS measure is beguiling in its simplicity, but it is limited in its ability to capture the full genetic loading for a disorder. We currently have an incomplete list of genetic variants associated with a disorder, and the effect sizes used to construct the score are imprecise. The use of tagging SNPs in place of the (unknown) causal variant or variants also limits precision, but a novel methodology has been developed, for example, extensions of the LDpred, in order to address this issue [18, 19]. Further, it is becoming clear that genetic risk scores also capture information from the environment. Evidence for this is seen in family-based studies which show that contributions from the PRS computed from non-transmitted alleles of parents also affect offspring phenotypes. This ‘genetic nurture’ phenomenon indicates, for example, that educational attainment is influenced by both offspring genetics and the non-transmitted parental genetics, which may determine the family environment [20].
