One of the most important observations to emerge is that almost all complex traits have a highly polygenic component to their variance: that is, their genetic basis consists of relatively frequent (> 5%) risk alleles at a very large number of loci, each making a small contribution to variation, or disease susceptibility. Across all diseases, the median odds ratio (OR, a measure of the extent to which a genotype, or allele, increases the risk of developing disease) is 1.25 This observation is drawn from the 1,736 studies in the National Human Genome Research Institute (NHGRI) catalog of published GWAS (564 studies of disease; accessed November 2013) [22]. Fewer than 2% of the observations have an OR greater than 2.5, and fewer than 1% have an OR greater than 4. Similarly, for quantitative traits, the amount of variance explained by a locus is much less than 0.5%. Even these estimates are likely upwardly biased due to the inclusion of smaller studies and Winner’s Curse effects [23].
