Variation in complex traits is almost invariably due to a combination of genetic and environmental factors. A useful quantification of the importance of genetic factors is the heritability (h2), i.e. the proportion of phenotypic variation in a trait that is due to genetic factors9 (BOX 1). Assuming that the estimated h2 is a true reflection of the population parameter, the upper limit of the phenotypic variance explained by a linear predictor (R2) based on DNA markers such as SNPs is h2 and a genetic predictor can thus never fully account for all phenotypic variation. This upper limit is only achievable if all genetic variants affecting the trait are known and their effects are estimated without error. In human disease genetics, where ‘personalised medicine’ is actively being pursued, this limitation is not well understood in our opinion and hence we have chosen to highlight it here, even though it has been pointed out before10, 11.
