We identified several associated SNPs in or near genes related to chromatin structure. In addition to HMGA2, which encodes a chromatin-binding protein, we found associations with a SNP (rs10946808) in a histone cluster on chromosome 6, a SNP (rs12986413) in the histone methyltransferase DOT1L gene and a SNP (rs724016) in an intron of the methyl-DNA-binding transcriptional repressor gene ZBTB38. It is currently unclear how genetic variation at these loci modulate height, but there is a precedent for a connection between regulation of chromatin structure and stature: Sotos syndrome (MIM117550), characterized by extreme tall stature, is caused by mutations and deletions in the histone methyltransferase gene NSD1. It would be interesting to test whether the height variants at HMGA2, the chromosome 6 histone cluster, DOT1L and ZBTB38 modify clinical outcome in Sotos syndrome, or whether severe mutations in these genes, particularly DOT1L, could cause a Sotos syndrome-like phenotype.
