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

Wendy Cozen, Dalin Li, Timothy Best, David J. Van Den Berg, Pierre Antoine Gourraud, Victoria K. Cortessis, Andrew D. Skol, Thomas M. Mack, Sally L. Glaser, Lawrence M. Weiss, Bharat N. Nathwani, Smita Bhatia, Fredrick R. Schumacher, Christopher K. Edlund, Amie E. Hwang, Susan L. Slager, Zachary S. Fredericksen, Louise C. Strong, Thomas M. Habermann, Brian K. LinkJames R. Cerhan, Leslie L. Robison, David V. Conti, Kenan Onel

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51 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)469-475
Number of pages7
JournalBlood
Volume119
Issue number2
DOIs
StatePublished - Jan 12 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Cozen, W., Li, D., Best, T., Van Den Berg, D. J., Gourraud, P. A., Cortessis, V. K., Skol, A. D., Mack, T. M., Glaser, S. L., Weiss, L. M., Nathwani, B. N., Bhatia, S., Schumacher, F. R., Edlund, C. K., Hwang, A. E., Slager, S. L., Fredericksen, Z. S., Strong, L. C., Habermann, T. M., ... Onel, K. (2012). A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood, 119(2), 469-475. https://doi.org/10.1182/blood-2011-03-343921