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  • Smedby, Karin E.Karolinska Institutet (author)

GWAS of Follicular Lymphoma Reveals Allelic Heterogeneity at 6p21.32 and Suggests Shared Genetic Susceptibility with Diffuse Large B-cell Lymphoma

  • Article/chapterEnglish2011

Publisher, publication year, extent ...

  • 2011-04-21
  • Public Library of Science (PLoS),2011
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-154280
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-154280URI
  • https://doi.org/10.1371/journal.pgen.1001378DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:122562197URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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 (ORcombined = 0.64, P-combined= 2x10(-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: ORadjusted = 0.70, P-adjusted= 4x10(-12); rs10484561: ORadjusted = 1.64, P-adjusted= 5x10(-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 (ORcombined = 1.36, P-combined = 1.4x10(-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.

Subject headings and genre

  • MEDICINE
  • MEDICIN

Added entries (persons, corporate bodies, meetings, titles ...)

  • Foo, Jia Nee (author)
  • Skibola, Christine F. (author)
  • Darabi, HatefKarolinska Institutet (author)
  • Conde, Lucia (author)
  • Hjalgrim, HenrikKarolinska Institutet (author)
  • Kumar, Vikrant (author)
  • Chang, Ellen T. (author)
  • Rothman, Nathaniel (author)
  • Cerhan, James R. (author)
  • Brooks-Wilson, Angela R. (author)
  • Rehnberg, Emil (author)
  • Irwan, Ishak D. (author)
  • Ryder, Lars P.Karolinska Institutet (author)
  • Brown, Peter N. (author)
  • Bracci, Paige M. (author)
  • Agana, Luz (author)
  • Riby, Jacques (author)
  • Cozen, Wendy (author)
  • Davis, Scott (author)
  • Hartge, Patricia (author)
  • Morton, Lindsay M. (author)
  • Severson, Richard K. (author)
  • Wang, Sophia S. (author)
  • Slager, Susan L. (author)
  • Fredericksen, Zachary S. (author)
  • Novak, Anne J. (author)
  • Kay, Neil E. (author)
  • Habermann, Thomas M. (author)
  • Armstrong, Bruce (author)
  • Kricker, Anne (author)
  • Milliken, Sam (author)
  • Purdue, Mark P. (author)
  • Vajdic, Claire M. (author)
  • Boyle, Peter (author)
  • Lan, Qing (author)
  • Zahm, Shelia H. (author)
  • Zhang, Yawei (author)
  • Zheng, Tongzhang (author)
  • Leach, Stephen (author)
  • Spinelli, John J. (author)
  • Smith, Martyn T. (author)
  • Chanock, Stephen J. (author)
  • Padyukov, Leonid (author)
  • Alfredsson, LarsKarolinska Institutet (author)
  • Klareskog, LarsKarolinska Institutet (author)
  • Glimelius, BengtUppsala universitet,Enheten för onkologi(Swepub:uu)bengglim (author)
  • Melbye, Mads (author)
  • Liu, Edison T. (author)
  • Adami, Hans-Olov (author)
  • Humphreys, KeithKarolinska Institutet (author)
  • Liu, Jianjun (author)
  • Karolinska InstitutetEnheten för onkologi (creator_code:org_t)

Related titles

  • In:PLoS Genetics: Public Library of Science (PLoS)7:4, s. e1001378-1553-73901553-7404

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