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Meta-Analysis
. 2012 Jan 12;119(2):469-75.
doi: 10.1182/blood-2011-03-343921. Epub 2011 Nov 15.

A Genome-Wide Meta-Analysis of Nodular Sclerosing Hodgkin Lymphoma Identifies Risk Loci at 6p21.32

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Free PMC article
Meta-Analysis

A Genome-Wide Meta-Analysis of Nodular Sclerosing Hodgkin Lymphoma Identifies Risk Loci at 6p21.32

Wendy Cozen et al. Blood. .
Free PMC article

Abstract

Nodular sclerosing Hodgkin lymphoma (NSHL) is a distinct, highly heritable Hodgkin lymphoma subtype. We undertook a genome-wide meta-analysis of 393 European-origin adolescent/young adult NSHL patients and 3315 controls using the Illumina Human610-Quad Beadchip and Affymetrix Genome-Wide Human SNP Array 6.0. We identified 3 single nucleotide polymorphisms (SNPs) on chromosome 6p21.32 that were significantly associated with NSHL risk: rs9268542 (P = 5.35 × 10(-10)), rs204999 (P = 1.44 × 10(-9)), and rs2858870 (P = 1.69 × 10(-8)). We also confirmed a previously reported association in the same region, rs6903608 (P = 3.52 × 10(-10)). rs204999 and rs2858870 were weakly correlated (r(2) = 0.257), and the remaining pairs of SNPs were not correlated (r(2) < 0.1). In an independent set of 113 NSHL cases and 214 controls, 2 SNPs were significantly associated with NSHL and a third showed a comparable odds ratio (OR). These SNPs are found on 2 haplotypes associated with NSHL risk (rs204999-rs9268528-rs9268542-rs6903608-rs2858870; AGGCT, OR = 1.7, P = 1.71 × 10(-6); GAATC, OR = 0.4, P = 1.16 × 10(-4)). All individuals with the GAATC haplotype also carried the HLA class II DRB1*0701 allele. In a separate analysis, the DRB1*0701 allele was associated with a decreased risk of NSHL (OR = 0.5, 95% confidence interval = 0.4, 0.7). These data support the importance of the HLA class II region in NSHL etiology.

Figures

Figure 1
Figure 1
Results of a meta-analysis of 2 GWAS on 393 cases and 3315 controls. (A) Manhattan plot of the genome-wide results. P values were determined for each SNP based on the meta-analysis of the UC and USC samples. Five SNPs surpassed the genome-wide significance threshold (P value = 5 × 10−8): rs9268542, rs9268528, rs204999, rs2858870, and rs6903608 6p21.3. (B) Regional plot of the 6p21.3 for the combined genome-wide association results. The blue lines represent recombination rates. The previously reported SNP rs6903608 is designated by a diamond; all other SNPs are depicted by circles. (C) Linkage disequilibrium map of the 6p21.3 region (red represents r2 > 0.9).

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