Briefly, there are three common complaints about the work of the PGC. First, “the results don’t matter” – the readouts are broad and the effect sizes of individual associated loci are small. In fact, as discussed above, the results are delivering increasingly useful and targeted knowledge (discussed under Aim 1 above) (44, 45, 54). The small effect sizes do not constrain the potential utility of targeting the identified genes or pathways – drugs targeting those pathways can have major effects. Small effects can identify “druggable” targets: the canonical example of this is that GWAS has identified common genetic variation of small effect for multiple cholesterol measures in a gene (HMGCR) whose protein is the target of a class of cholesterol-lowering medication (46). Unlike 10 years ago, pharmaceutical companies are following this area closely as genomic data are increasingly crucial to drug development (46).
