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A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass

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Abstract

Osteoporosis is a highly heritable common bone disease leading to fractures that severely impair the life quality of patients. Wrist fractures caused by osteoporosis are largely due to the scarcity of wrist bone mass. Here we report the results of a genome-wide association study (GWAS) of wrist bone mineral density (BMD). We examined ∼500000 SNP markers in 1000 unrelated homogeneous Caucasian subjects and found a novel allelic association with wrist BMD at rs11023787 in the SOX6 (SRY (sex determining region Y)-box 6) gene (P=9.00×10−5). Subjects carrying the C allele of rs11023787 in SOX6 had significantly higher mean wrist BMD values than those with the T allele (0.485:0.462 g cm−2 for C allele vs. T allele carriers). For validation, we performed SOX6 association for BMD in an independent Chinese sample and found that SNP rs11023787 was significantly associated with wrist BMD in the Chinese sample (P=6.41×10−3). Meta-analyses of the GWAS scan and the replication studies yielded P-values of 5.20×10−6 for rs11023787. Results of this study, together with the functional relevance of SOX6 in cartilage formation, support the SOX6 gene as an important gene for BMD variation.

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Authors and Affiliations

  1. Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, 410081, China

    LiJun Tan, Rong Liu, ShuFeng Lei, Rong Pan, Fang Yang & HongWen Deng

  2. Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, Kansas City, MO, 64108, USA

    LiJun Tan, ShuFeng Lei & HongWen Deng

  3. Institute of Molecular Genetics, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, China

    TieLin Yang, Han Yan, YuFang Pei, Feng Zhang, Feng Pan & YinPin Zhang

  4. College of Life Sciences and Bioengineering, Beijing Jiaotong University, Beijing, 100044, China

    HongGang Hu & HongWen Deng

  5. Vanderbilt Microarray Shared Resource, Vanderbilt University, Nashville, TN, 37232, USA

    Shawn Levy

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  1. LiJun Tan
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Correspondence to HongWen Deng.

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Tan, L., Liu, R., Lei, S. et al. A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass. Sci. China Life Sci. 53, 1065–1072 (2010). https://doi.org/10.1007/s11427-010-4056-7

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  • DOI: https://doi.org/10.1007/s11427-010-4056-7

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