It has been argued that the biological information emerging from GWA studies will become less relevant as sample sizes increase, because as thousands of associated variants are discovered, the range of implicated genes and pathways will lose specificity and cover essentially the entire genome20. If this were the case, then increasing sample sizes would not help to prioritize follow up studies aimed at identifying and understanding new biology, and the associated loci would blanket the entire genome. Our study provides strong evidence to the contrary: the identification of many 100’s and even 1000’s of associated variants can continue to provide biologically relevant information. In other words, the variants identified in larger sample sizes both display a stronger enrichment of pathways clearly relevant to skeletal growth and prioritize many additional new and relevant genes. Furthermore, the associated variants are often non-randomly and tightly clustered (typically separated by <250 kb), resulting in the frequent presence of multiple associated variants in a locus. The observations that genes and especially pathways are now beginning to be implicated by multiple variants suggests that the larger
