It is perhaps not surprising that many variants conferring a low risk of a complex disease effect a change of quantity in gene expression, because many of these diseases can be thought of as quantitative traits themselves, with disease diagnosis being made when a clinical threshold is surpassed (as is the case with hypertension and Alzheimer’s disease). This frequent observation from genomewide association studies was presaged by the observation that genetic variability in the insulin-gene promoter is associated with an increased risk of type 1 diabetes.25
