rs7108738

This study examined rare variants near EN1 and common variants near SOX6 for associations with pediatric bone mineral density in 1,418 children and adolescents (733 females, 685 males). The rare T allele of rs11692564 (EN1) was associated with higher bone density at the total hip (beta=0.62, p=9.0×10⁻⁴) and femoral neck (beta=0.53, p=0.010), with much stronger effects in females (total hip beta=0.86, p=6.6×10⁻⁶). The common G allele of rs11024028 (SOX6) was also associated with higher bone density, with differences in skeletal sites between sexes, suggesting early-life genetic mechanisms underlying osteoporosis risk.

This fine-mapping association study identified 20 SNPs in the SOX6 gene significantly associated with hip bone mineral density (BMD) across Caucasian and Chinese populations. The most significant SNP was rs1347677 (P=3.15×10⁻⁷) located in intron 3, associated with reduced hip BMD (beta=-0.0173 to -0.0094). The previously reported SNP rs7117858 was successfully replicated (P=2.45×10⁻⁴). Notably, the association showed skeletal site specificity with no significant associations detected for spine BMD.