The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature

To examine 51 single nucleotide polymorphisms (SNPs) corresponding to the 46 previously reported genomic loci for height in 8,184 European American children with height measurements. We leveraged genotyping data from our ongoing GWA study of height variation in children in order to query the 51 SNPs in this pediatric cohort.Sixteen of these SNPs yielded at least nominally significant association to height, representing fifteen different loci including EFEMP1-PNPT1, GPR126, C6orf173, SPAG17, Histone class 1, HLA class III and GDF5-UQCC. Other loci revealed no evidence for association, including HMGA1 and HMGA2. For the 16 associated variants, the genotype score explained 1.64% of the total variation for height z-score.Among 46 loci that have been reported to associate with adult height to date, at least 15 also contribute to the determination of height in childhood.Height has been correlated with various disorders, including the observations that taller people are at a higher risk of developing cancer and shorter people are more likely to present with type 2 diabetes [1-3]. Determination of height in humans has long been considered to be largely influenced by genetic factors; indeed, twin and family studies have suggested that as much as 90% of variation in human height is genetically determined[4-8].For many years, studies have attempted to identify genetic factors influencing human height in order to provide insights into human growth and development. Prior to 2007, genome-wide linkage and candidate-gene association studies had limited success in this regard; however, with the recent emergence of genome wide association (GWA) studies, tens of common genetics variants influencing height have now been uncovered, primarily in adults[9-14].Weedon et al published the first GWA study of height using the Affymetrix GeneChip Human Mapping 500 K platform on nearly 5,000 individuals of self-reported European ancestry[9]. As a consequence, they observed association to common