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Meta-analysis identifies a MECOM gene as a novel predisposing factor of osteoporotic fracture
  1. Joo-Yeon Hwang1,
  2. Seung Hun Lee2,3,
  3. Min Jin Go1,
  4. Beom-Jun Kim2,3,
  5. Ikuyo Kou4,
  6. Shiro Ikegawa4,
  7. Yan Guo5,
  8. Hong-Wen Deng5,
  9. Soumya Raychaudhuri6,7,
  10. Young Jin Kim1,
  11. Ji Hee Oh1,
  12. Youngdoe Kim1,
  13. Sanghoon Moon1,
  14. Dong-Joon Kim1,
  15. Heejo Koo1,
  16. My-Jung Cha1,
  17. Min Hye Lee1,
  18. Ji Young Yun1,
  19. Hye-Sook Yoo1,
  20. Young-Ah Kang1,
  21. Eun-Hee Cho8,
  22. Sang-Wook Kim8,
  23. Ki Won Oh9,
  24. Moo Il Kang10,
  25. Ho Young Son10,
  26. Shin-Yoon Kim3,11,
  27. Ghi Su Kim2,3,
  28. Bok-Ghee Han1,
  29. Yoon Shin Cho1,12,
  30. Myeong-Chan Cho13,
  31. Jong-Young Lee1,
  32. Jung-Min Koh2,3
  1. 1Center for Genome Science, National Institute of Health, Chungcheongbuk-do, Republic of Korea
  2. 2Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
  3. 3Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Republic of Korea
  4. 4Laboratory for Bone and Joint Disease, SNP Research center, RIKEN, Minato-ku, Tokyo, Japan
  5. 5Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, PR China
  6. 6Divisions of Genetics and Rheumatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
  7. 7Medical and Population Genetics Program, Broad Institute, Cambridge, Massachusetts, USA
  8. 8Department of Internal Medicine, Kangwon National University College of Medicine, Chuncheon, Republic of Korea
  9. 9Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  10. 10Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea
  11. 11Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
  12. 12Department of Biomedical Science, Hallym University, Chuncheon, Gangwon-do, Republic of Korea
  13. 13National Institute of Health, Chungcheongbuk-do, Republic of Korea
  1. Correspondence to Jong-Young Lee, Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Chungbuk 363-951, Republic of Korea; leejy63{at} or Dr Jung-Min Koh, Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Republic of Korea; jmkoh{at}


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.

  • Osteoporosis

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