Abstract:
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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 etiology are still limited given the rare occurrence of the disease. In this study, we investigated in a family trio dataset that consists 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 SNP-level summary statistics obtained from a likelihood ratio test of the trio data, utilizing 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 indicated that osteosarcoma is potentially related to TP53, estrogen receptor signaling, and xenobiotic metabolism signaling.
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