A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2018-05-01
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| Series: | Cancer Informatics |
| Online Access: | https://doi.org/10.1177/1176935118775103 |
| _version_ | 1818351296616333312 |
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| author | Yi Yang Saonli Basu Lisa Mirabello Logan Spector Lin Zhang |
| author_facet | Yi Yang Saonli Basu Lisa Mirabello Logan Spector Lin Zhang |
| author_sort | Yi Yang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T18:35:29Z |
| format | Article |
| id | doaj.art-b9d185330c9944d6a114fbba5072ee52 |
| institution | Directory Open Access Journal |
| issn | 1176-9351 |
| language | English |
| last_indexed | 2024-12-13T18:35:29Z |
| publishDate | 2018-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cancer Informatics |
| spelling | doaj.art-b9d185330c9944d6a114fbba5072ee522022-12-21T23:35:22ZengSAGE PublishingCancer Informatics1176-93512018-05-011710.1177/1176935118775103A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured PriorYi YangSaonli BasuLisa MirabelloLogan SpectorLin ZhangOsteosarcoma 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.https://doi.org/10.1177/1176935118775103 |
| spellingShingle | Yi Yang Saonli Basu Lisa Mirabello Logan Spector Lin Zhang A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior Cancer Informatics |
| title | A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior |
| title_full | A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior |
| title_fullStr | A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior |
| title_full_unstemmed | A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior |
| title_short | A Bayesian Gene-Based Genome-Wide Association Study Analysis of Osteosarcoma Trio Data Using a Hierarchically Structured Prior |
| title_sort | bayesian gene based genome wide association study analysis of osteosarcoma trio data using a hierarchically structured prior |
| url | https://doi.org/10.1177/1176935118775103 |
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