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Previous studies have linked the WNT pathway and human skeleton formation; therefore, genes related to WNT might contribute to the onset and development of osteoporosis. In this study, we investigated the potential genetic association of  WLS , which encodes an important mediator in the WNT pathway, with osteoporosis and its related quantitative traits in a sample of 6,620 individuals from Han Chinese population. A two-stage approach, with a discovery stage with 859 cases and 1,690 controls and a validation stage with 1,039 cases and 3,032 controls, was applied in the study. Forty SNPs were genotyped in the discovery stage. The intronic SNP rs2566752 was identified to be significantly associated with osteoporosis (OR discovery  = 0.78,  P   discovery  = 3.73 × 10 −5 ; OR validation  = 0.80,  P   validation  = 1.96 × 10 −5 ). Two SNPs surrounding rs2566752 (in addition to this SNP itself) were identified to be associated with bone mineral density. In addition, we have identified a 20 kb peak region of H3K27Ac histone mark enrichment between rs2772304 and rs2566752. Our study suggested that  WLS  is an important locus for osteoporosis and its related quantitative phenotypes in Han Chinese population. Additional sequencing-based studies are needed to investigate the genetic architecture of this regulatory region and its relationship with osteoporosis-related phenotypes.

Genetic association study identified a 20 kb regulatory element in WLS associated with osteoporosis and bone mineral density in Han Chinese