Genome-wide Association Study Identification of a New Genetic Locus with Susceptibility to Osteoporotic Fracture in the Korean Population

ABSTRACT

Osteoporotic fracture (OF), along with bone mineral density (BMD), is an important diagnostic parameter and a clinical predictive risk factor in the assessment of osteoporosis in the elderly population. However, a genomewide association study (GWAS) on OF has not yet been clarified sufficiently. To identify OF-associated genetic variants and candidate genes, we conducted a GWAS in a population-based cohort (Korean Association Resource [KARE], n=1,427 [case: 288 and control: 1139]) and performed a de novo replication study in hospital-based individuals (Asan and Catholic Medical Center [ACMC], n=1,082 [case: 272 and control: 810]). In a combined meta-analysis, a newly identified genetic locus in an intergenic region at 10p11.2 (near genes FZD8 and ANKRD30A ) showed the most significant association (odd ratio [OR] = 2.00, 95% confidence interval [CI] = 1.47~2.74, p=1.27x10(-5)) in the same direction. We provide the first evidence for a common genetic variant influencing OF and genetic information for further investigation in bone metabolism.