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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE58718 | GEO | 2014/09/23

SECONDARY ACCESSION(S): PRJNA253226

REPOSITORIES: GEO

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Project description:Within the framework of the International Lymphoma Epidemiology Consortium (InterLymph) Consortium and NCI-sponsored Cohort Consortium, investigators from 22 studies came together to conduct a genome-wide association study (GWAS) of non-Hodgkin lymphoma (NHL). The goal of the study was to identify common genetic variants associated with the risk of NHL. As described previously (Berndt SI et al., Nature Genetics, 2013, PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/?term=23770605">23770605</a> ), cases and controls from 22 studies, including nine prospective cohort studies, eight population-based case-control studies, and five clinic or hospital-based case-control studies were included in this effort. Cases of NHL were ascertained from cancer registries, clinics or hospitals, or through self-report verified by medical and pathology reports. The phenotype information for all NHL cases was reviewed centrally at the InterLymph Data Coordinating Center and harmonized according to the hierarchical classification proposed by the InterLymph Pathology Working Group based on the World Health Organization (WHO) classification (2008). Controls were frequency matched to cases on age and gender by study, and the study was limited to subjects of European ancestry. Participants were genotyped using the Illumina Omni Express. The NCI Non-Hodgkin Lymphoma GWAS is utilized in the following dbGaP sub-studies. To view genotypes and derived variables collected in these sub-studies, please click on the following sub-studies below or in the "Sub-studies" box located on the right hand side of this top-level study page <a href="study.cgi?study_id=phs000801">phs000801</a> NCI Non-Hodgkin Lymphoma GWAS. <ul> <li><a href="study.cgi?study_id=phs000802">phs000802</a> NCI Non-Hodgkin Lymphoma GWAS: CLL</li> <li><a href="study.cgi?study_id=phs000818">phs000818</a> NCI Non-Hodgkin Lymphoma GWAS: Controls</li> <li><a href="study.cgi?study_id=phs000889">phs000889</a> NCI Non-Hodgkin Lymphoma GWAS: DLBCL</li> <li><a href="study.cgi?study_id=phs000890">phs000890</a> NCI Non-Hodgkin Lymphoma GWAS: FL</li> <li><a href="study.cgi?study_id=phs000891">phs000891</a> NCI Non-Hodgkin Lymphoma GWAS: MZL</li> </ul>

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

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