A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass
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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.
Keywordsosteoporosis GWAS SOX6 SNPs wrist BMD
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- 1.Ray N F, Chan J K, Thamer M, et al. Medical expenditures for the treatment of osteoporotic fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res, 1997, 12: 24–35 1:STN:280:DyaK2szot1Oguw%3D%3D, 10.1359/jbmr.1922.214.171.124, 9240722PubMedCrossRefGoogle Scholar
- 2.Public Health Service Office of the Surgeon General Public Health Service Office of the Surgeon General. 2004Google Scholar
- 12.Macdonald H M, McGuigan F E, Stewart A, et al. Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women. J Bone Miner Res, 2006, 21: 151–162 1:CAS:528:DC%2BD28Xpt1SmsA%3D%3D, 10.1359/JBMR.050906, 16355284PubMedCrossRefGoogle Scholar
- 13.Ralston S H, Uitterlinden A G, Brandi M L, et al. Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS, 2006, 14: 943–951Google Scholar
- 20.Weir B. Genetic Data Analysis III. Sunderland: Sinauer Associates, 2007Google Scholar