PMID- 21533074
OWN - NLM
STAT- MEDLINE
DCOM- 20110812
LR  - 20240211
IS  - 1553-7404 (Electronic)
IS  - 1553-7390 (Print)
IS  - 1553-7390 (Linking)
VI  - 7
IP  - 4
DP  - 2011 Apr
TI  - GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests 
      shared genetic susceptibility with diffuse large B-cell lymphoma.
PG  - e1001378
LID - 10.1371/journal.pgen.1001378 [doi]
LID - e1001378
AB  - Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological 
      malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A 
      previous genome-wide association study has established a marker, rs10484561 in 
      the human leukocyte antigen (HLA) class II region on 6p21.32 associated with 
      increased FL risk. Here, in a three-stage genome-wide association study, starting 
      with a genome-wide scan of 379 FL cases and 791 controls followed by validation 
      in 1,049 cases and 5,790 controls, we identified a second independent 
      FL-associated locus on 6p21.32, rs2647012 (OR(combined)  = 0.64, P(combined)  = 2 
      x 10(-21)) located 962 bp away from rs10484561 (r(2)<0.1 in controls). After 
      mutual adjustment, the associations at the two SNPs remained genome-wide 
      significant (rs2647012:OR(adjusted)  = 0.70, P(adjusted)  =  4 x 10(-12); 
      rs10484561:OR(adjusted)  = 1.64, P(adjusted)  = 5 x 10(-15)). Haplotype and 
      coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct 
      haplotype from that of rs10484561 and tags a novel allele with an opposite 
      (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 
      FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was 
      associated with risk of diffuse large B-cell lymphoma (OR(combined)  = 1.36, 
      P(combined)  =  1.4 x 10(-7)). Our results reveal the presence of allelic 
      heterogeneity within the HLA class II region influencing FL susceptibility and 
      indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. 
      These findings suggest that the HLA class II region plays a complex yet important 
      role in NHL.
FAU - Smedby, Karin E
AU  - Smedby KE
AD  - Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, 
      Stockholm, Sweden.
FAU - Foo, Jia Nee
AU  - Foo JN
FAU - Skibola, Christine F
AU  - Skibola CF
FAU - Darabi, Hatef
AU  - Darabi H
FAU - Conde, Lucia
AU  - Conde L
FAU - Hjalgrim, Henrik
AU  - Hjalgrim H
FAU - Kumar, Vikrant
AU  - Kumar V
FAU - Chang, Ellen T
AU  - Chang ET
FAU - Rothman, Nathaniel
AU  - Rothman N
FAU - Cerhan, James R
AU  - Cerhan JR
FAU - Brooks-Wilson, Angela R
AU  - Brooks-Wilson AR
FAU - Rehnberg, Emil
AU  - Rehnberg E
FAU - Irwan, Ishak D
AU  - Irwan ID
FAU - Ryder, Lars P
AU  - Ryder LP
FAU - Brown, Peter N
AU  - Brown PN
FAU - Bracci, Paige M
AU  - Bracci PM
FAU - Agana, Luz
AU  - Agana L
FAU - Riby, Jacques
AU  - Riby J
FAU - Cozen, Wendy
AU  - Cozen W
FAU - Davis, Scott
AU  - Davis S
FAU - Hartge, Patricia
AU  - Hartge P
FAU - Morton, Lindsay M
AU  - Morton LM
FAU - Severson, Richard K
AU  - Severson RK
FAU - Wang, Sophia S
AU  - Wang SS
FAU - Slager, Susan L
AU  - Slager SL
FAU - Fredericksen, Zachary S
AU  - Fredericksen ZS
FAU - Novak, Anne J
AU  - Novak AJ
FAU - Kay, Neil E
AU  - Kay NE
FAU - Habermann, Thomas M
AU  - Habermann TM
FAU - Armstrong, Bruce
AU  - Armstrong B
FAU - Kricker, Anne
AU  - Kricker A
FAU - Milliken, Sam
AU  - Milliken S
FAU - Purdue, Mark P
AU  - Purdue MP
FAU - Vajdic, Claire M
AU  - Vajdic CM
FAU - Boyle, Peter
AU  - Boyle P
FAU - Lan, Qing
AU  - Lan Q
FAU - Zahm, Shelia H
AU  - Zahm SH
FAU - Zhang, Yawei
AU  - Zhang Y
FAU - Zheng, Tongzhang
AU  - Zheng T
FAU - Leach, Stephen
AU  - Leach S
FAU - Spinelli, John J
AU  - Spinelli JJ
FAU - Smith, Martyn T
AU  - Smith MT
FAU - Chanock, Stephen J
AU  - Chanock SJ
FAU - Padyukov, Leonid
AU  - Padyukov L
FAU - Alfredsson, Lars
AU  - Alfredsson L
FAU - Klareskog, Lars
AU  - Klareskog L
FAU - Glimelius, Bengt
AU  - Glimelius B
FAU - Melbye, Mads
AU  - Melbye M
FAU - Liu, Edison T
AU  - Liu ET
FAU - Adami, Hans-Olov
AU  - Adami HO
FAU - Humphreys, Keith
AU  - Humphreys K
FAU - Liu, Jianjun
AU  - Liu J
LA  - eng
GR  - N01 PC067009/CN/NCI NIH HHS/United States
GR  - N01 PC067010/PC/NCI NIH HHS/United States
GR  - P42 ES004705/ES/NIEHS NIH HHS/United States
GR  - N01 PC067008/PC/NCI NIH HHS/United States
GR  - R01 CA122663/CA/NCI NIH HHS/United States
GR  - R01 CA062006/CA/NCI NIH HHS/United States
GR  - N01 PC065064/PC/NCI NIH HHS/United States
GR  - R01 CA104682/CA/NCI NIH HHS/United States
GR  - R01 CA092153/CA/NCI NIH HHS/United States
GR  - R01 CA045614/CA/NCI NIH HHS/United States
GR  - U01 CA118444/CA/NCI NIH HHS/United States
GR  - R03 CA089745/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20110421
PL  - United States
TA  - PLoS Genet
JT  - PLoS genetics
JID - 101239074
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Chromosomes, Human, Pair 6/*genetics
MH  - Denmark
MH  - Gene Frequency
MH  - *Genetic Predisposition to Disease
MH  - Genetic Variation
MH  - Genome, Human
MH  - Genome-Wide Association Study
MH  - Haplotypes
MH  - Histocompatibility Antigens Class II/*genetics
MH  - Humans
MH  - Lymphoma, Follicular/*genetics
MH  - Lymphoma, Large B-Cell, Diffuse/*genetics
MH  - Polymorphism, Single Nucleotide
MH  - Risk Factors
MH  - Sweden
PMC - PMC3080853
COIS- The authors have declared that no competing interests exist.
EDAT- 2011/05/03 06:00
MHDA- 2011/08/13 06:00
PMCR- 2011/04/01
CRDT- 2011/05/03 06:00
PHST- 2010/09/24 00:00 [received]
PHST- 2011/03/18 00:00 [accepted]
PHST- 2011/05/03 06:00 [entrez]
PHST- 2011/05/03 06:00 [pubmed]
PHST- 2011/08/13 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - 10-PLGE-RA-NV-4214R2 [pii]
AID - 10.1371/journal.pgen.1001378 [doi]
PST - ppublish
SO  - PLoS Genet. 2011 Apr;7(4):e1001378. doi: 10.1371/journal.pgen.1001378. Epub 2011 
      Apr 21.