Summary of the copy number variation (CNV) analysis by lymphoma subtype.

<p>Summary of the copy number variation (CNV) analysis by lymphoma subtype.</p

Copy Number Variation Analysis on a Non-Hodgkin Lymphoma Case-Control Study Identifies an 11q25 Duplication Associated with Diffuse Large B-Cell Lymphoma

<div><p>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 <i>LOC283177</i> long non-coding RNA that was further confirmed 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.</p></div

The figure shows, on the top, the aberrations (deletions in red, duplications in green) found in the 11q25 region in controls and DLBCL cases after CNV analysis using a genotyping array.

<p>On the bottom, the figure shows the locations of the 9 PCR primers designed to cover the LOC283177 gene. qPCR confirmed the partial duplication of LOC283177 (P = 0.004), and the region of breakpoint was determined to be located between primers P4 and P5. Coordinates are shown with respect to the NCBI36/hg18 assembly.</p

Association results and linkage disequilibrium in <i>MSH3</i>.

<p><i>r</i>² values for our genotyped samples are shown in the top section (“<i>r²</i> values in NHL data”) and <i>r</i>² from the CEU population of HapMap are shown in the bottom section (“<i>r²</i> values in HapMap CEU data”). The gene model of <i>MSH3</i> is shown on top, 5′ to 3′ from left to right, with vertical lines marking exons. <i>p</i>-values (before correction for multiple testing) are from the analysis in DLBCL samples of European ancestry.</p

Logistic regression analysis results for SNPs with <i>p_G</i><0.05.

*<p>Coordinates obtained from Ensembl 64.</p

Genes and categories.

<p>Genes and categories.</p

Ten-year risks of pancreatic cancer (y-axis), by age, gender, and risk score percentile (x-axis).

<p>The risk score includes smoking history, heavy alcohol intake, BMI, history of diabetes, family history of pancreatic cancer, ABO genotype and three common genetic variants associated with pancreatic cancer.</p

Reclassification of lifetime risk of pancreatic cancer after adding genetic information to the risk model with both genetic and non-genetic covariates.

<p>Reclassification of lifetime risk of pancreatic cancer after adding genetic information to the risk model with both genetic and non-genetic covariates.</p

Participants' Characteristics, the PanScan Consortium.

<p>Participants' Characteristics, the PanScan Consortium.</p

Reclassification of lifetime risk of pancreatic cancer among cohort controls after adding genetic information to the risk model.

<p>Reclassification of lifetime risk of pancreatic cancer among cohort controls after adding genetic information to the risk model.</p