A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass
A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass
复制标题
全基因组关联分析表明 SOX6 是腕骨量的候选基因
DOI：
10.1007/s11427-010-4056-7
复制
发表时间：
2010-09-01
影响因子：
9.1
通讯作者：
Deng HongWen
中科院分区：
文献类型：
--
作者：
Tan LiJun;Liu Rong;Deng HongWen
骨质疏松症是一种高度遗传性的常见骨病，可导致骨折，严重影响患者的生活质量。骨质疏松引起的手腕骨折很大程度上是由于手腕骨量稀缺造成的。在这里，我们报告了腕骨矿物质密度 (BMD) 的全基因组关联研究 (GWAS) 的结果。我们在 1000 名不相关的同质白人受试者中检查了约 500000 个 SNP 标记，发现 SOX6（SRY（性别决定区 Y）-box 6）基因中的 rs11023787 处与腕部 BMD 存在新的等位基因关联（P=9.00×10(-5)）。携带 SOX6 rs11023787 的 C 等位基因的受试者的平均手腕 BMD 值显着高于携带 T 等位基因的受试者（C 等位基因与 T 等位基因携带者为 0.485:0.462 g cm(-2)）。为了验证，我们在一个独立的中国样本中对 BMD 进行了 SOX6 关联，发现 SNP rs11023787 与中国样本中的腕部 BMD 显着相关（P=6.41×10(-3)）。 GWAS 扫描和复制研究的荟萃分析得出 rs11023787 的 P 值为 5.20×10(-6)。这项研究的结果以及 SOX6 在软骨形成中的功能相关性，支持 SOX6 基因作为 BMD 变异的重要基因。
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.