Struan F.A. Grant^1,2,3, Mingyao Li⁴, Jonathan P. Bradfield¹, Cecilia E. Kim¹, Kiran Annaiah¹, Erin Santa¹, Joseph T. Glessner¹, Tracy Casalunovo¹, Edward C. Frackelton¹, F. George Otieno¹, Julie L. Shaner¹, Ryan M. Smith¹, Andrew W. Eckert¹, Marcin Imielinski¹, Rosetta M. Chiavacci¹, Robert I. Berkowitz^5,6 and Hakon Hakonarson^1,2,3

¹Center for Applied Genomics, Abramson Research Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, U.S.A. ²Department of Pediatrics and Division of Human Genetics, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, U.S.A. ³Department of Pediatrics University of Pennsylvania, School of Medicine, Philadelphia, Pennsylvania 19104, U.S.A. ⁴Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, U.S.A. ⁵Behavioral Health Center and Department of Child and Adolescent Psychiatry, The Children’s Hospital of Philadelphia, Philadelphia PA 19104, U.S.A. ⁶Center for Weight and Eating Disorders, Department of Psychiatry, University of Pennsylvania, Philadelphia PA 19104, U.S.A.

Abstract

Background: Recently an association was demonstrated between the single nucleotide polymorphism (SNP), rs1042725, within the HMGA2 locus and height as a consequence of a genome wide association (GWA) study of this trait in adults; this observation was also reported in children aged 7–11 years old.

Objective: We examined in our Caucasian childhood cohort the effects of two strong surrogates for this SNP at this locus with height, rs8756 and rs7968902, with respect to the same pediatric age category but also in children grouped separately as younger and older.

Methods: Utilizing data from an ongoing GWA study in our cohort of 2,619 Caucasian children with measurements for height, we investigated the association of the previously reported variation at the HMGA2 locus with this height treated as a quantitative trait (age and sex corrected) in childhood in the 2–6 (n = 706), 7–11 (n = 617) and 12–18 (n = 1293) years old categories.

Results: The minor alleles of rs8756 and rs7968902 respectively (strong surrogates for rs1042725 i.e. r2 = 0.873 and 0.761 in the CEU HapMap respectively) were significantly associated with height in the 7–11 years old age group (P = 3.53 × 10−3 and 2.82 × 10−4, respectively). However in the 2–6 and 12–18 years old age groups, no association was observed.

Conclusions: We observe a strong association with height in same age group of 7–11 years old as has been previously reported. However, in the under 7s and the over 11s, no such association was observed.