Meta analysis identifies a novel susceptibility locus associated with heel bone strength in the Korean population

Abstract

Introduction Calcaneal quantitative ultrasound has been recognized as a non-invasive method for evaluation of bone strength and prediction of osteoporotic fracture.

Methods To extend a thorough genetic catalog for osteoporotic bone properties, we performed a genome-wide association study (rural cohort I, n = 1895) of speed of sound (SOS) using the 1000 genome-based imputation in the discovery stage and then carried out in silico lookups (rural cohort II and III, n = 2,967) and de novo genotyping (rural cohort IV, n = 4,296) in the replication stage.

Results In the combined meta-analysis (n = 9,158), we identified a novel variant associated with SOS (rs2445771 in the GLDN gene, P = 2.27 × 10− 9) reaching genome-wide significance in the Korean population. We further demonstrated that allele-specific regulatory modifications found to be associated with functional enrichments by ENCODE annotations. Conclusion: Our findings could provide additional insights into understanding of genetic and epigenetic regulations on bone metabolism.