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 Matthew Habermann, Brian K. Link & 4 others James R Cerhan, Leslie L. Robison, David V. Conti, Kenan Onel

Research output: Contribution to journalArticle

45 Citations (Scopus)

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

Fingerprint

Polymorphism
Hodgkin Disease
Meta-Analysis
Nucleotides
Genes
Genome
Single Nucleotide Polymorphism
Odds Ratio
Chromosomes
Haplotypes
Alleles
Human Genome
Young Adult
Confidence Intervals

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Cozen, W., Li, D., Best, T., Van Den Berg, D. J., Gourraud, P. A., Cortessis, V. K., ... 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

A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. / Cozen, Wendy; Li, Dalin; Best, Timothy; Van Den Berg, David J.; Gourraud, Pierre Antoine; Cortessis, Victoria K.; Skol, Andrew D.; Mack, Thomas M.; Glaser, Sally L.; Weiss, Lawrence M.; Nathwani, Bharat N.; Bhatia, Smita; Schumacher, Fredrick R.; Edlund, Christopher K.; Hwang, Amie E.; Slager, Susan L; Fredericksen, Zachary S.; Strong, Louise C.; Habermann, Thomas Matthew; Link, Brian K.; Cerhan, James R; Robison, Leslie L.; Conti, David V.; Onel, Kenan.

In: Blood, Vol. 119, No. 2, 12.01.2012, p. 469-475.

Research output: Contribution to journalArticle

Cozen, W, Li, D, Best, T, Van Den Berg, DJ, Gourraud, PA, Cortessis, VK, Skol, AD, Mack, TM, Glaser, SL, Weiss, LM, Nathwani, BN, Bhatia, S, Schumacher, FR, Edlund, CK, Hwang, AE, Slager, SL, Fredericksen, ZS, Strong, LC, Habermann, TM, Link, BK, Cerhan, JR, Robison, LL, Conti, DV & Onel, K 2012, 'A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32', Blood, vol. 119, no. 2, pp. 469-475. https://doi.org/10.1182/blood-2011-03-343921
Cozen W, Li D, Best T, Van Den Berg DJ, Gourraud PA, Cortessis VK et al. A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. Blood. 2012 Jan 12;119(2):469-475. https://doi.org/10.1182/blood-2011-03-343921
Cozen, Wendy ; Li, Dalin ; Best, Timothy ; Van Den Berg, David J. ; Gourraud, Pierre Antoine ; Cortessis, Victoria K. ; Skol, Andrew D. ; Mack, Thomas M. ; Glaser, Sally L. ; Weiss, Lawrence M. ; Nathwani, Bharat N. ; Bhatia, Smita ; Schumacher, Fredrick R. ; Edlund, Christopher K. ; Hwang, Amie E. ; Slager, Susan L ; Fredericksen, Zachary S. ; Strong, Louise C. ; Habermann, Thomas Matthew ; Link, Brian K. ; Cerhan, James R ; Robison, Leslie L. ; Conti, David V. ; Onel, Kenan. / A genome-wide meta-analysis of nodular sclerosing Hodgkin lymphoma identifies risk loci at 6p21.32. In: Blood. 2012 ; Vol. 119, No. 2. pp. 469-475.
@article{bacbf0fb5d604e0e88891880d8d37e4a,
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.",
author = "Wendy Cozen and Dalin Li and Timothy Best and {Van Den Berg}, {David J.} and Gourraud, {Pierre Antoine} and Cortessis, {Victoria K.} and Skol, {Andrew D.} and Mack, {Thomas M.} and Glaser, {Sally L.} and Weiss, {Lawrence M.} and Nathwani, {Bharat N.} and Smita Bhatia and Schumacher, {Fredrick R.} and Edlund, {Christopher K.} and Hwang, {Amie E.} and Slager, {Susan L} and Fredericksen, {Zachary S.} and Strong, {Louise C.} and Habermann, {Thomas Matthew} and Link, {Brian K.} and Cerhan, {James R} and Robison, {Leslie L.} and Conti, {David V.} and Kenan Onel",
year = "2012",
month = "1",
day = "12",
doi = "10.1182/blood-2011-03-343921",
language = "English (US)",
volume = "119",
pages = "469--475",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "2",

}

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 Matthew

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 (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.

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 (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.

UR - http://www.scopus.com/inward/record.url?scp=84862910604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862910604&partnerID=8YFLogxK

U2 - 10.1182/blood-2011-03-343921

DO - 10.1182/blood-2011-03-343921

M3 - Article

VL - 119

SP - 469

EP - 475

JO - Blood

JF - Blood

SN - 0006-4971

IS - 2

ER -