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

Abstract

Calcaneal quantitative ultrasound has been recognized as a non-invasive method for evaluation of bone strength and prediction of osteoporotic fracture. 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. 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. Our findings could provide additional insights into understanding of genetic and epigenetic regulations on bone metabolism.