Copy number variation analysis on a non-Hodgkin lymphoma case-control study identifies an 11q25 duplication associated with diffuse large B-cell lymphoma

Recent GWAS have identified several susceptibility loci for NHL. Despite these successes, much of the heritable variation in NHL risk remains to be explained. Common copy-number variants are important genomic sources of variability, and hence a potential source to explain part of this missing heritability. In this study, we carried out a CNV analysis using GWAS data from 681 NHL cases and 749 controls to explore the relationship between common structural variation and lymphoma susceptibility. Here we found a novel association with diffuse large B-cell lymphoma (DLBCL) risk involving a partial duplication of the C-terminus region of the LOC283177 long non-coding RNA that was further validated by quantitative PCR. For chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), known somatic deletions were identified on chromosomes 13q14, 11q22-23, 14q32 and 22q11.22. Our study shows that GWAS data can be used to identify germline CNVs associated with disease risk for DLBCL and somatic CNVs for CLL/SLL. We performed a genome-wide CNV analysis of 681 NHL cases and 749 controls from the San Francisco Bay Area, genotyped using the Illumina HumanCNV370-Duo BeadChip array. Signal intensity data in the form of log R ratio (LRR) and B allele frequency (BAF) values were obtained directly from the Beadstudio software. Quality control filtering was used to exclude unreliable samples, resulting in a final dataset of 619 NHL cases (205 FL, 242 DLBCL, 172 CLL/SLL) and 730 controls.