META-ANALYSIS IDENTIFIES A NOVEL LOCUS ASSOCIATED WITH QUANTITATIVE ULTRASOUND 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=2.27x10 -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.