title: A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32.
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.
authors.affiliation: Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. wcozen@usc.edu
authors.forename: Wendy
authors.initials: W
authors.lastname: Cozen
authors.forename: Dalin
authors.initials: D
authors.lastname: Li
authors.forename: Timothy
authors.initials: T
authors.lastname: Best
authors.forename: David J
authors.initials: DJ
authors.lastname: Van Den Berg
authors.forename: Pierre-Antoine
authors.initials: PA
authors.lastname: Gourraud
authors.forename: Victoria K
authors.initials: VK
authors.lastname: Cortessis
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Skol
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Mack
authors.forename: Sally L
authors.initials: SL
authors.lastname: Glaser
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Weiss
authors.forename: Bharat N
authors.initials: BN
authors.lastname: Nathwani
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
authors.forename: Fredrick R
authors.initials: FR
authors.lastname: Schumacher
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Edlund
authors.forename: Amie E
authors.initials: AE
authors.lastname: Hwang
authors.forename: Susan L
authors.initials: SL
authors.lastname: Slager
authors.forename: Zachary S
authors.initials: ZS
authors.lastname: Fredericksen
authors.forename: Louise C
authors.initials: LC
authors.lastname: Strong
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Habermann
authors.forename: Brian K
authors.initials: BK
authors.lastname: Link
authors.forename: James R
authors.initials: JR
authors.lastname: Cerhan
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.forename: David V
authors.initials: DV
authors.lastname: Conti
authors.forename: Kenan
authors.initials: K
authors.lastname: Onel
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics*; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D055815:Young Adult
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