a phenomenon that has triggered much discussion about the underlying reasons, which might include a great number of small effect variants, gene-gene interactions, multiple individually rare variables that are not detectable by GWAS, copy number variations (a type of variation that remains incompletely examined although it represents a significant fraction of inter-individual variation) and perhaps epigenetic variation (16, 21, 22). Whichever the case, it is our view that the fact that they explain little of the phenotypic variance takes nothing away from the value of the identified associations. Knowing a gene is involved in a disease provides knowledge about the disease mechanisms and potential therapeutic targets, especially once the relationship between the DNA variants and the gene’s function in the relevant pathways is determined. Although the normally occurring variation within a gene might influence the risk only by little, pharmacological intervention targeting that gene’s function could have a significant impact. For example, although genetic associations between PPAR gamma and diabetes mellitus are relatively weak, with odds ratios below 1.2 (23), PPAR gamma is the target of thiazolidinediones, a class of oral antidiabetic agents (24). Another striking example is the LDL receptor where, while mutations only account for a small fraction
