The contribution of genetic variants to disease depends on the ruler

Our understanding of the genetic basis of disease has evolved from descriptions of overall heritability or familiality to the identification of large numbers of risk loci. One can quantify the impact of such loci on disease using a plethora of measures, which can guide future research decisions. However, different measures can attribute varying degrees of importance to a variant. In this Analysis, we consider and contrast the most commonly used measures - specifically, the heritability of disease liability, approximate heritability, sibling recurrence risk, overall genetic variance using a logarithmic relative risk scale, the area under the receiver-operating curve for risk prediction and the population attributable fraction - and give guidelines for their use that should be explicitly considered when assessing the contribution of genetic variants to disease.