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将先验基因集信息整合到全基因组关联研究中。

Integration of a priori gene set information into genome-wide association studies.

作者信息

Sohns Melanie, Rosenberger Albert, Bickeböller Heike

机构信息

Department of Genetic Epidemiology, University Medical Center Göttingen, Humboldtallee 32, 37073 Göttingen, Germany.

出版信息

BMC Proc. 2009 Dec 15;3 Suppl 7(Suppl 7):S95. doi: 10.1186/1753-6561-3-S7-S95.

DOI:10.1186/1753-6561-3-S7-S95
PMID:20018092
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2795999/
Abstract

In genome-wide association studies (GWAS) genetic markers are often ranked to select genes for further pursuit. Especially for moderately associated and interrelated genes, information on genes and pathways may improve the selection. We applied and combined two main approaches for data integration to a GWAS for rheumatoid arthritis, gene set enrichment analysis (GSEA) and hierarchical Bayes prioritization (HBP). Many associated genes are located in the HLA region on 6p21. However, the ranking lists of genes and gene sets differ considerably depending on the chosen approach: HBP changes the ranking only slightly and primarily contains HLA genes in the top 100 gene lists. GSEA includes also many non-HLA genes.

摘要

在全基因组关联研究(GWAS)中,遗传标记常常被排序以选择基因进行进一步研究。特别是对于中度关联和相互关联的基因,基因和通路的信息可能会改善选择。我们将两种主要的数据整合方法——基因集富集分析(GSEA)和层次贝叶斯优先级排序(HBP)应用于类风湿性关节炎的GWAS并进行了结合。许多相关基因位于6号染色体短臂21区的HLA区域。然而,根据所选方法的不同,基因和基因集的排名列表有很大差异:HBP仅略微改变排名,并且在前100个基因列表中主要包含HLA基因。GSEA还包括许多非HLA基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b68/2795999/26c72658153f/1753-6561-3-S7-S95-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b68/2795999/26c72658153f/1753-6561-3-S7-S95-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b68/2795999/26c72658153f/1753-6561-3-S7-S95-1.jpg

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本文引用的文献

1
On the utility of gene set methods in genomewide association studies of quantitative traits.基因集方法在数量性状全基因组关联研究中的效用
Genet Epidemiol. 2008 Nov;32(7):658-68. doi: 10.1002/gepi.20334.
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Pathway-based approaches for analysis of genomewide association studies.基于通路的全基因组关联研究分析方法。
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Hierarchical Bayes prioritization of marker associations from a genome-wide association scan for further investigation.基于全基因组关联扫描的标记关联分层贝叶斯优先级排序以进行进一步研究。
一种用于在逻辑核机器测试中校正大小偏差的新型核及其在类风湿性关节炎中的应用。
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BMC Proc. 2009 Dec 15;3 Suppl 7(Suppl 7):S94. doi: 10.1186/1753-6561-3-s7-s94.
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Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50. doi: 10.1073/pnas.0506580102. Epub 2005 Sep 30.