Finally, there is the argument that there truly is missing heritability in GWAS studies. It is little appreciated that GWAS do not actually measure heritability (the ratio of genetic to total phenotypic variance in a population) but rather they measure just the genetic variance. Missing heritability is inferred with respect to heritability estimates that generally derive from family studies, where ironically direct estimates of the genetic contribution are lacking. Consequently, it is difficult to actually estimate how much of the variance GWAS-captured variants should explain in outbred populations. However, in the case of height, where heritability is as high as 80%, over 50% of the phenotype can be attributed to common variants using the mixed linear modeling approach71, and after adjustment for allele frequency skews and incomplete LD, essentially the entire genetic contribution has been ascribed to genotypic variation. Yet the same methods applied to BMI do not capture much more than half of the expected genotypic variance, and it is not clear that they are as efficient for schizophrenia, arthritis or intelligence75,76. In these cases, it can be argued
