Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture

Background: Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. Methods: Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. Results: In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF (rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10^-8; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. Conclusions: Our findings provide new insights into the genetic architecture underlying OF in East Asians.