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

Hwang,  Joo Yeon; Lee,  Seung Hun; Go,  Min Jin; Kim,  Beom Jun; Kim,  Young Jin; Kim,  Dong Joon; Oh,  Ji Hee; Koo,  Heejo; Cha,  My Jung; Lee,  Min Hye; Yun,  Ji Young; Yoo,  Hye Sook; Kang,  Young Ah; Oh,  Ki Won; Kang,  Moo Il; Son,  Ho Young; Kim,  Shin Yoon; Kim,  Ghi Su; Han,  Bok Ghee; Cho,  Yoon Shin; Koh,  Jung Min; Lee,  Jong Young

doi:2011.9.2.52

Genomics Inform > Volume 9(2); 2011 > Article

Original Article

Genomics & Informatics 2011;9(2): 52-58.

DOI: https://doi.org/10.5808/gi.2011.9.2.52

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

Joo Yeon Hwang, Seung Hun Lee, Min Jin Go, Beom Jun Kim, Young Jin Kim, Dong Joon Kim, Ji Hee Oh, Heejo Koo, My Jung Cha, Min Hye Lee, Ji Young Yun, Hye Sook Yoo, Young Ah Kang, Ki Won Oh, Moo Il Kang, Ho Young Son, Shin Yoon Kim, Ghi Su Kim, Bok Ghee Han, Yoon Shin Cho, Jung Min Koh, Jong Young Lee

¹Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungbuk 363-951, Korea. leejy63@nih.go.kr
²Division of Endocrinology and Metabolism, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea.
³Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu 700-721, Korea.
⁴Department of Internal Medicine, Sungkyunkwan University School of Medicine, Seoul 136-710, Korea.
⁵Department of Internal Medicine, The Catholic University of Korea School of Medicine, Seoul 137-701, Korea.
⁶Department of Orthopedic Surgery, School of Medicine, Kyungpook National University, Daegu 700-721, Korea.

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.

Keywords: genomewide association study; meta-analysis; osteoporotic fracture; intergenic