Journal of Medical Genetics, 2013, 01, 212─219

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

Hwang JY, Lee SH, Go MJ, Kim BJ, Kou I, Ikegawa S, Guo Y, Deng HW, Raychaudhuri S, Kim YJ, Oh JH, Kim Y, Moon S, Kim DJ, Koo H, Cha MJ, Lee MH, Yun JY, Yoo HS, Kang YA, Cho EH, Kim SW, Oh KW, Kang MI, Son HY, Kim SY, Kim GS, Han BG, Cho YS, Cho MC, Lee JY, Koh JM

Abstract

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

• ISBN or ISSN: 1468-6244

• 본 연구는 질병관리본부 연구개발과제(과제번호 2012-N73005-00) 연구비를 지원받아 수행되었습니다.
• This research was supported by a fund(code 2012-N73005-00) by Research of Korea Centers for Disease Control and Prevention.