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bioRxiv · 10.1101/017657

Tissue-specific Enrichment of Lymphoma Risk Loci in Regulatory Elements

James E Hayes·Gosia Trynka·Joseph Vijai·Kenneth Offit·Soumya Raychaudhuri·Robert Klein
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Abstract

Though numerous polymorphisms have been associated with risk of developing lymphoma, how these variants function to promote tumorigenesis is poorly understood. Here, we report that lymphoma risk SNPs, especially in the non-Hodgkins lymphoma subtype chronic lymphocytic leukemia, are significantly enriched for co-localization with epigenetic marks of active gene regulation. These enrichments were seen in a lymphoid-specific manner for numerous ENCODE datasets, including DNase-hypersensitivity as well as multiple segmentation-defined enhancer regions. Furthermore, we identify putatively functional SNPs that are both in regulatory elements in lymphocytes and are associated with gene expression changes in blood. We developed an algorithm, UES, that uses a Monte Carlo simulation approach to calculate the enrichment of previously identified risk SNPs in various functional elements. This multiscale approach integrating multiple datasets helps disentangle the underlying biology of lymphoma, and more broadly, is generally applicable to GWAS results from other diseases as well.

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James E Hayes, Gosia Trynka, Joseph Vijai, Kenneth Offit, Soumya Raychaudhuri, Robert Klein. 2015-04-07. Tissue-specific Enrichment of Lymphoma Risk Loci in Regulatory Elements. https://doi.org/10.1101/017657

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