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A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32
- 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.
- Subjects :
- Adult
Male
Adolescent
Clinical Trials and Observations
Immunology
Genome-wide association study
Single-nucleotide polymorphism
Human leukocyte antigen
Biology
Polymorphism, Single Nucleotide
Biochemistry
Young Adult
Risk Factors
Polymorphism (computer science)
Humans
Genetic Predisposition to Disease
Allele
Child
Genetics
Haplotype
Cell Biology
Hematology
Odds ratio
Middle Aged
Hodgkin Disease
Haplotypes
Case-Control Studies
Child, Preschool
Chromosomes, Human, Pair 6
Female
Genome-Wide Association Study
SNP array
Subjects
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