Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture. Issue 4 (24th January 2013)

• Record Type: Journal Article
• Authors: Hwang, Joo-Yeon; Lee, Seung Hun; Go, Min Jin; Kim, Beom-Jun; Kou, Ikuyo; Ikegawa, Shiro; Guo, Yan; Deng, Hong-Wen; Raychaudhuri, Soumya; Kim, Young Jin; Oh, Ji Hee; Kim, Youngdoe; Moon, Sanghoon; Kim, Dong-Joon; Koo, Heejo; Cha, My-Jung; Lee, Min Hye; Yun, Ji Young; Yoo, Hye-Sook; Kang, Young-Ah; Cho, Eun-Hee; Kim, Sang-Wook; Oh, Ki Won; Kang, Moo Il; Son, Ho Young; Kim, Shin-Yoon; Kim, Ghi Su; Han, Bok-Ghee; Cho, Yoon Shin; Cho, Myeong-Chan; Lee, Jong-Young; Koh, Jung-Min;
• Is Part Of: Journal of medical genetics. Volume 50:Issue 4(2013)
• Page Start: 212
• Page End: 219
• Publication Date: 2013-01-24
• Subjects: Osteoporosis; Medical genetics -- Periodicals; 616.042
• DOI: 10.1136/jmedgenet-2012-101156
• Languages: English
• ISSNs: 1468-6244

Abstract

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.