Abstract

Recent genome-wide association studies have identified a novel polymorphism, rs1042725, in the HMGA2 gene for human adult height, a highly heritable complex trait. Replications in independent populations are needed to evaluate a positive finding and determine its generality. Thus, we performed a replication study to examine the associations between polymorphisms in HMGA2 and adult height in two US Caucasian populations (an unrelated sample of 998 subjects and a family-based sample of 8385 subjects) and a Chinese population (1638 unrelated Han subjects). We confirmed the association between rs1042725 in HMGA2 and adult height both in the unrelated and family-based Caucasian populations (overall P= 4.25 x 10(-9)). Another two SNPs (rs7968902 and rs7968682), which were in high linkage disequilibrium with rs1042725, also achieved the significance level in both Caucasian populations (overall P= 6.34 x 10(-7), and 2.72 x 10(-9), respectively). Our results provide strong support to the initial finding. Moreover, SNP rs1042725 was firstly found to be associated with adult height (P= 0.008) in the Chinese population, and the effect is in the same direction as in the Caucasian populations, suggesting that it is a common variant across different populations. Our study further highlights the importance of the HMGA2 gene's involvement in normal growth.