RT Journal Article
SR Electronic
T1 Tissue-specific Enrichment of Lymphoma Risk Loci in Regulatory Elements
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 017657
DO 10.1101/017657
A1 James E. Hayes
A1 Gosia Trynka
A1 Joseph Vijai
A1 Kenneth Offit
A1 Soumya Raychaudhuri
A1 Robert J. Klein
YR 2015
UL http://biorxiv.org/content/early/2015/04/07/017657.abstract
AB 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.