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A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32

Authors :
Dalin Li
Christopher K. Edlund
Pierre-Antoine Gourraud
Susan L. Slager
Victoria K. Cortessis
Louise C. Strong
Leslie L. Robison
Kenan Onel
James R. Cerhan
David Van Den Berg
Timothy Best
David V. Conti
Thomas M. Habermann
Andrew D. Skol
Zachary S. Fredericksen
Lawrence M. Weiss
Fredrick R. Schumacher
Brian K. Link
Wendy Cozen
Bharat N. Nathwani
Thomas M. Mack
Amie E. Hwang
Smita Bhatia
Sally L. Glaser
Source :
Blood. 119:469-475
Publication Year :
2012
Publisher :
American Society of Hematology, 2012.

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 (r2 = 0.257), and the remaining pairs of SNPs were not correlated (r2 < 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.

Details

ISSN :
15280020 and 00064971
Volume :
119
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....d2a06e879e4ee7f25ab7f4b3d49bf0d8
Full Text :
https://doi.org/10.1182/blood-2011-03-343921