Two of the novel loci are located near genes that seem particularly relevant to height. rs584438 is located approximately 500 bp upstream of IGFBP4, which codes for insulin-like growth factor binding protein 4, and is in linkage disequilibrium (r2=0.87) with another SNP (rs598892) that results in a synonymous amino acid change in IGFBP4. IGFBP4 binds to IGF1 and IGF2,42 which have an important role in childhood growth. In blood, this same SNP showed a significant association with the expression of TNS4 (Supplementary Table 8), which interacts with beta-catenin,43 a critical component of the canonical Wnt pathway related to bone formation.44 The height SNP rs2362965 lies 285 kb from SHOX2, a homolog to the X-linked, pseudoautosomal SHOX (short stature homeobox) gene family, which plays a major role in skeletal limb development.
