Tissue-Specific Enrichment of Lymphoma Risk Loci in Regulatory Elements.

PLoS One
Authors
Keywords
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-Hodgkin's 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.

Year of Publication
2015
Journal
PLoS One
Volume
10
Issue
9
Pages
e0139360
Date Published
2015
ISSN
1932-6203
URL
DOI
10.1371/journal.pone.0139360
PubMed ID
26422229
PubMed Central ID
PMC4589387
Links
Grant list
P30 CA008748 / CA / NCI NIH HHS / United States
U01 HG007033 / HG / NHGRI NIH HHS / United States