That the variant rs1042725, strongly associated with adult and childhood height12, falls in the 3′ UTR of HMGA2 is notable in part because HMGA2 is the human gene with the greatest number of validated let-7 microRNA binding sites24,25. In fact, rs1042725 is 13 base pairs away from a let-7 site, suggesting a possible mechanism of action whereby the SNP alters microRNA binding and therefore expression of HMGA2. When we examined our list of 12 height loci, we were somewhat surprised to find three additional previously described targets of let-7: the cell cycle regulator CDK6 (ref. 26), the histone methyltransferase DOT1L27 and the gene LIN28B28. PAPPA, a locus with a combined P = 1.2 × 10-6 in our study, also contains a predicted let-7 binding site27. Thus, genes that influence height seem to be enriched for validated or potential let-7 targets: 5 of the 16 (31%) confirmed or suggestive loci associated with height have let-7 binding sites, compared with 2% of the genes in the human genome (Fisher’s exact test P = 3 × 10-5). Because microRNAs can co-regulate genes involved
