TY - JOUR
T1 - A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32
AU - Cozen, Wendy
AU - Li, Dalin
AU - Best, Timothy
AU - Van Den Berg, David J.
AU - Gourraud, Pierre Antoine
AU - Cortessis, Victoria K.
AU - Skol, Andrew D.
AU - Mack, Thomas M.
AU - Glaser, Sally L.
AU - Weiss, Lawrence M.
AU - Nathwani, Bharat N.
AU - Bhatia, Smita
AU - Schumacher, Fredrick R.
AU - Edlund, Christopher K.
AU - Hwang, Amie E.
AU - Slager, Susan L.
AU - Fredericksen, Zachary S.
AU - Strong, Louise C.
AU - Habermann, Thomas M.
AU - Link, Brian K.
AU - Cerhan, James R.
AU - Robison, Leslie L.
AU - Conti, David V.
AU - Onel, Kenan
PY - 2012/1/12
Y1 - 2012/1/12
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2011-03-343921
DO - 10.1182/blood-2011-03-343921
M3 - Article
C2 - 22086417
AN - SCOPUS:84862910604
SN - 0006-4971
VL - 119
SP - 469
EP - 475
JO - Blood
JF - Blood
IS - 2
ER -