Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease.
Genome-wide association study identifies COL2A1 locus involved in the hand development failure of Kashin-Beck disease.
复制标题
全基因组关联研究确定了与大骨节病手部发育障碍有关的 COL2A1 位点
DOI：
10.1038/srep40020
复制
发表时间：
2017-01-06
影响因子：
4.6
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Hao J;Wang W;Wen Y;Xiao X;He A;Wu C;Wang S;Guo X;Zhang F
大骨节病是一种慢性骨软骨病。大骨节病手部生长发育障碍的发病机制至今仍不清楚。本研究对493例大骨节病患者手掌长宽比进行了两阶段全基因组关联研究。应用Affytelm全基因组人类SNP阵列6.0对90例大骨节病患者进行全基因组SNP分型。关联分析采用PLINK。通过IMPUTE对1000基因组计划的参考组进行插补分析。在403名大骨节病患者的独立验证样本中选择两个SNP进行复制。在GWAS的发现中，观察到手掌LWR与COL2A1基因的rs2071358之间存在显著关联（P值= 4.68 × 10−8）。此外，GWAS检测到COL2A1基因rs4760608处的提示关联信号（P值= 1.76 × 10−4）。COL2A1的插补分析进一步鉴定了2个与手掌LWR相关的SNP。复制研究发现COL2A1基因的rs2071358（P值= 0.017）和rs4760608（P值= 0.002）均存在显著的关联信号。综合前人的研究结果，我们认为COL2A1可能是大骨节病手发育障碍的易感基因。
Kashin-Beck disease (KBD) is a chronic osteochondropathy. The pathogenesis of growth and development failure of hand of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally including 493 study subjects. Affymetrix Genome Wide Human SNP Array 6.0 was applied for genome-wide SNP genotyping of 90 KBD patients. Association analysis was conducted by PLINK. Imputation analysis was performed by IMPUTE against the reference panel of the 1000 genome project. Two SNPs were selected for replication in an independent validation sample of 403 KBD patients. In the discovery GWAS, significant association was observed between palmar LWR and rs2071358 of COL2A1 gene (Pvalue = 4.68 × 10−8). In addition, GWAS detected suggestive association signal at rs4760608 of COL2A1 gene (Pvalue = 1.76 × 10−4). Imputation analysis of COL2A1 further identified 2 SNPs with association evidence for palmar LWR. Replication study observed significant association signals at both rs2071358 (Pvalue = 0.017) and rs4760608 (Pvalue = 0.002) of COL2A1 gene. Based on previous and our study results, we suggest that COL2A1 was a likely susceptibility gene involved in the hand development failure of KBD.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
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影响因子：
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2.9
作者：
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McAlinden A
影响因子：
2.7
作者：
Xiong, G
通讯作者：
Xiong, G