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Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

Ferreiro-Iglesias, Aida; Lesseur, Corina; McKay, James; Hung, Rayjean J.; Han, Younghun; Zong, Xuchen; Christiani, David; Johansson, Mattias; Xiao, Xiangjun and Li, Yafang, et al. (2018) In Nature Communications 9(1).
Abstract

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are... (More)

Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA–tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.

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Nature Communications
volume
9
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1
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Nature Publishing Group
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  • scopus:85053845843
ISSN
2041-1723
DOI
10.1038/s41467-018-05890-2
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English
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76b70b44-2df4-423a-80aa-0b92fc13a828
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2018-10-08 13:19:54
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2019-08-14 04:24:18
@article{76b70b44-2df4-423a-80aa-0b92fc13a828,
  abstract     = {<p>Lung cancer has several genetic associations identified within the major histocompatibility complex (MHC); although the basis for these associations remains elusive. Here, we analyze MHC genetic variation among 26,044 lung cancer patients and 20,836 controls densely genotyped across the MHC, using the Illumina Illumina OncoArray or Illumina 660W SNP microarray. We impute sequence variation in classical HLA genes, fine-map MHC associations for lung cancer risk with major histologies and compare results between ethnicities. Independent and novel associations within HLA genes are identified in Europeans including amino acids in the HLA-B*0801 peptide binding groove and an independent HLA-DQB1*06 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB1*0401 and HLA-DRB1*0701; the latter better represented by the amino acid Ala-104. These results implicate several HLA–tumor peptide interactions as the major MHC factor modulating lung cancer susceptibility.</p>},
  articleno    = {3927},
  author       = {Ferreiro-Iglesias, Aida and Lesseur, Corina and McKay, James and Hung, Rayjean J. and Han, Younghun and Zong, Xuchen and Christiani, David and Johansson, Mattias and Xiao, Xiangjun and Li, Yafang and Qian, David C. and Ji, Xuemei and Liu, Geoffrey and Caporaso, Neil and Scelo, Ghislaine and Zaridze, David and Mukeriya, Anush and Kontic, Milica and Ognjanovic, Simona and Lissowska, Jolanta and Szołkowska, Małgorzata and Swiatkowska, Beata and Janout, Vladimir and Holcatova, Ivana and Bolca, Ciprian and Savic, Milan and Ognjanovic, Miodrag and Bojesen, Stig Egil and Wu, Xifeng and Albanes, Demetrios and Aldrich, Melinda C. and Tardon, Adonina and Fernandez-Somoano, Ana and Fernandez-Tardon, Guillermo and Le Marchand, Loic and Rennert, Gadi and Chen, Chu and Doherty, Jennifer and Goodman, Gary and Bickeböller, Heike and Wichmann, H. Erich and Risch, Angela and Rosenberger, Albert and Shen, Hongbing and Dai, Juncheng and Field, John K. and Davies, Michael and Woll, Penella and Teare, M. Dawn and Kiemeney, Lambertus A. and van der Heijden, Erik H.F.M. and Yuan, Jian Min and Hong, Yun Chul and Haugen, Aage and Zienolddiny, Shanbeh and Lam, Stephen and Tsao, Ming Sound and Johansson, Mikael and Grankvist, Kjell and Schabath, Matthew B. and Andrew, Angeline and Duell, Eric and Melander, Olle and Brunnström, Hans and Lazarus, Philip and Arnold, Susanne and Slone, Stacey and Byun, Jinyoung and Kamal, Ahsan and Zhu, Dakai and Landi, Maria Teresa and Amos, Christopher I. and Brennan, Paul},
  issn         = {2041-1723},
  language     = {eng},
  number       = {1},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity},
  url          = {http://dx.doi.org/10.1038/s41467-018-05890-2},
  volume       = {9},
  year         = {2018},
}