A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior.
A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior.
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DOI：
10.1177/1176935118775103
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发表时间：
2018
影响因子：
2
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Yang Y;Basu S;Mirabello L;Spector L;Zhang L
骨肉瘤被认为是儿童和年轻人中最常见的原发恶性骨癌。以前的研究表明，生长迅速和身高是骨肉瘤的危险因素。然而，考虑到这种疾病的罕见发生，对遗传原因的研究仍然有限。在这项研究中，我们在一个由209名患者及其未受影响的父母组成的家庭三人数据集中进行了调查，并进行了全基因组关联研究(Gwas)以确定骨肉瘤的遗传危险因素。我们根据单核苷酸多态(SNP)水平的汇总统计数据执行了基于贝叶斯基因的GWA，该统计数据是从三个数据的似然比检验获得的，该检验使用了结合了SNP基因分层结构的分层结构的先验。由于测试次数的减少，贝叶斯方法比SNP水平的GWAS分析具有更高的能力，并且通过考虑SNP之间的相关性而健壮，因此它可以跨基因内的SNPs借用信息。我们确定了217个具有全基因组意义的基因。基因集的独创性通路分析表明，骨肉瘤可能与破骨细胞中的TP53、雌激素受体信号、异种代谢信号和RANK信号有关。
Osteosarcoma is considered to be the most common primary malignant bone cancer among children and young adults. Previous studies suggest growth spurts and height to be risk factors for osteosarcoma. However, studies on the genetic cause are still limited given the rare occurrence of the disease. In this study, we investigated in a family trio data set that is composed of 209 patients and their unaffected parents and conducted a genome-wide association study (GWAS) to identify genetic risk factors for osteosarcoma. We performed a Bayesian gene-based GWAS based on the single-nucleotide polymorphism (SNP)-level summary statistics obtained from a likelihood ratio test of the trio data, which uses a hierarchically structured prior that incorporates the SNP-gene hierarchical structure. The Bayesian approach has higher power than SNP-level GWAS analysis due to the reduced number of tests and is robust by accounting for the correlations between SNPs so that it borrows information across SNPs within a gene. We identified 217 genes that achieved genome-wide significance. Ingenuity pathway analysis of the gene set indicated that osteosarcoma is potentially related to TP53, estrogen receptor signaling, xenobiotic metabolism signaling, and RANK signaling in osteoclasts.