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

Aida Ferreiro-Iglesias; Corina Lesseur; James McKay; Rayjean J Hung; Younghun Han; Xuchen Zong; David Christiani; Mattias Johansson; Xiangjun Xiao; Yafang Li; David C Qian; Xuemei Ji; Geoffrey Liu; Neil Caporaso; Ghislaine Scelo; David Zaridze; Anush Mukeriya; Milica Kontic; Simona Ognjanovic; Jolanta Lissowska; Małgorzata Szołkowska; Beata Swiatkowska; Vladimir Janout; Ivana Holcatova; Ciprian Bolca; Milan Savic; Miodrag Ognjanovic; Stig Egil Bojesen; Xifeng Wu; Demetrios Albanes; Melinda C Aldrich; Adonina Tardon; Ana Fernandez-Somoano; Guillermo Fernandez-Tardon; Loic Le Marchand; Gadi Rennert; Chu Chen; Jennifer Doherty; Gary Goodman; Heike Bickeböller; H-Erich Wichmann; Angela Risch; Albert Rosenberger; Hongbing Shen; Juncheng Dai; John K Field; Michael Davies; Penella Woll; M Dawn Teare; Lambertus A Kiemeney; Erik H F M van der Heijden; Jian-Min Yuan; Yun-Chul Hong; Aage Haugen; Shanbeh Zienolddiny; Stephen Lam; Ming-Sound Tsao; Mikael Johansson; Kjell Grankvist; Matthew B Schabath; Angeline Andrew; Eric Duell; Olle Melander; Hans Brunnström; Philip Lazarus; Susanne Arnold; Stacey Slone; Jinyoung Byun; Ahsan Kamal; Dakai Zhu; Maria Teresa Landi; Christopher I Amos; Paul Brennan

doi:10.1038/s41467-018-05890-2

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

Aida Ferreiro-Iglesias, Corina Lesseur, James McKay, Rayjean J Hung, Younghun Han, Xuchen Zong, David Christiani, Mattias Johansson, Xiangjun Xiao, Yafang Li, David C Qian, Xuemei Ji, Geoffrey Liu, Neil Caporaso, Ghislaine Scelo, David Zaridze, Anush Mukeriya, Milica Kontic, Simona Ognjanovic, Jolanta LissowskaMałgorzata Szołkowska, Beata Swiatkowska, Vladimir Janout, Ivana Holcatova, Ciprian Bolca, Milan Savic, Miodrag Ognjanovic, Stig Egil Bojesen, Xifeng Wu, Demetrios Albanes, Melinda C Aldrich, Adonina Tardon, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Loic Le Marchand, Gadi Rennert, Chu Chen, Jennifer Doherty, Gary Goodman, Heike Bickeböller, H-Erich Wichmann, Angela Risch, Albert Rosenberger, Hongbing Shen, Juncheng Dai, John K Field, Michael Davies, Penella Woll, M Dawn Teare, Lambertus A Kiemeney, Erik H F M van der Heijden, Jian-Min Yuan, Yun-Chul Hong, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Ming-Sound Tsao, Mikael Johansson, Kjell Grankvist, Matthew B Schabath, Angeline Andrew, Eric Duell, Olle Melander, Hans Brunnström, Philip Lazarus, Susanne Arnold, Stacey Slone, Jinyoung Byun, Ahsan Kamal, Dakai Zhu, Maria Teresa Landi, Christopher I Amos, Paul Brennan

Department of Clinical Medicine

15 Citations (Scopus)

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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 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.

Original language	English
Article number	3927
Journal	Nature Communications
Volume	9
Number of pages	12
ISSN	2041-1723
DOIs	https://doi.org/10.1038/s41467-018-05890-2
Publication status	Published - 1 Dec 2018

Keywords

Asian Continental Ancestry Group/genetics
Chromosome Mapping
European Continental Ancestry Group/genetics
Female
Gene Frequency
Genetic Predisposition to Disease/ethnology
Genotype
HLA Antigens/genetics
Humans
Lung Neoplasms/ethnology
Major Histocompatibility Complex/genetics
Male
Middle Aged
Peptides/genetics
Polymorphism, Single Nucleotide

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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s41467-018-05890-2Final published version, 1.96 MBLicence: CC BY

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Ferreiro-Iglesias, A., Lesseur, C., McKay, J., Hung, R. J., Han, Y., Zong, X., Christiani, D., Johansson, M., Xiao, X., Li, Y., Qian, D. C., Ji, X., Liu, G., Caporaso, N., Scelo, G., Zaridze, D., Mukeriya, A., Kontic, M., Ognjanovic, S., ... Brennan, P. (2018). Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity. Nature Communications, 9, Article 3927. https://doi.org/10.1038/s41467-018-05890-2

Ferreiro-Iglesias, A, Lesseur, C, McKay, J, Hung, RJ, Han, Y, Zong, X, Christiani, D, Johansson, M, Xiao, X, Li, Y, Qian, DC, Ji, X, Liu, G, Caporaso, N, Scelo, G, Zaridze, D, Mukeriya, A, Kontic, M, Ognjanovic, S, Lissowska, J, Szołkowska, M, Swiatkowska, B, Janout, V, Holcatova, I, Bolca, C, Savic, M, Ognjanovic, M, Bojesen, SE, Wu, X, Albanes, D, Aldrich, MC, Tardon, A, Fernandez-Somoano, A, Fernandez-Tardon, G, Le Marchand, L, Rennert, G, Chen, C, Doherty, J, Goodman, G, Bickeböller, H, Wichmann, H-E, Risch, A, Rosenberger, A, Shen, H, Dai, J, Field, JK, Davies, M, Woll, P, Teare, MD, Kiemeney, LA, van der Heijden, EHFM, Yuan, J-M, Hong, Y-C, Haugen, A, Zienolddiny, S, Lam, S, Tsao, M-S, Johansson, M, Grankvist, K, Schabath, MB, Andrew, A, Duell, E, Melander, O, Brunnström, H, Lazarus, P, Arnold, S, Slone, S, Byun, J, Kamal, A, Zhu, D, Landi, MT, Amos, CI & Brennan, P 2018, 'Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity', Nature Communications, vol. 9, 3927. https://doi.org/10.1038/s41467-018-05890-2

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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 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.",

keywords = "Asian Continental Ancestry Group/genetics, Chromosome Mapping, European Continental Ancestry Group/genetics, Female, Gene Frequency, Genetic Predisposition to Disease/ethnology, Genotype, HLA Antigens/genetics, Humans, Lung Neoplasms/ethnology, Major Histocompatibility Complex/genetics, Male, Middle Aged, Peptides/genetics, Polymorphism, Single Nucleotide",

author = "Aida Ferreiro-Iglesias and Corina Lesseur and James McKay and Hung, {Rayjean J} and Younghun Han and Xuchen Zong and David Christiani and Mattias Johansson and Xiangjun Xiao and Yafang Li and Qian, {David C} and Xuemei Ji and Geoffrey Liu and Neil Caporaso and Ghislaine Scelo and David Zaridze and Anush Mukeriya and Milica Kontic and Simona Ognjanovic and Jolanta Lissowska and Ma{\l}gorzata Szo{\l}kowska and Beata Swiatkowska and Vladimir Janout and Ivana Holcatova and Ciprian Bolca and Milan Savic and Miodrag Ognjanovic and Bojesen, {Stig Egil} and Xifeng Wu and Demetrios Albanes and Aldrich, {Melinda C} and Adonina Tardon and Ana Fernandez-Somoano and Guillermo Fernandez-Tardon and {Le Marchand}, Loic and Gadi Rennert and Chu Chen and Jennifer Doherty and Gary Goodman and Heike Bickeb{\"o}ller and H-Erich Wichmann and Angela Risch and Albert Rosenberger and Hongbing Shen and Juncheng Dai and Field, {John K} and Michael Davies and Penella Woll and Teare, {M Dawn} and Kiemeney, {Lambertus A} and {van der Heijden}, {Erik H F M} and Jian-Min Yuan and Yun-Chul Hong and Aage Haugen and Shanbeh Zienolddiny and Stephen Lam and Ming-Sound Tsao and Mikael Johansson and Kjell Grankvist and Schabath, {Matthew B} and Angeline Andrew and Eric Duell and Olle Melander and Hans Brunnstr{\"o}m and Philip Lazarus and Susanne Arnold and Stacey Slone and Jinyoung Byun and Ahsan Kamal and Dakai Zhu and Landi, {Maria Teresa} and Amos, {Christopher I} and Paul Brennan",

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doi = "10.1038/s41467-018-05890-2",

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journal = "Nature Communications",

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T1 - Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

AU - Ferreiro-Iglesias, Aida

AU - Lesseur, Corina

AU - McKay, James

AU - Hung, Rayjean J

AU - Han, Younghun

AU - Zong, Xuchen

AU - Christiani, David

AU - Johansson, Mattias

AU - Xiao, Xiangjun

AU - Li, Yafang

AU - Qian, David C

AU - Ji, Xuemei

AU - Liu, Geoffrey

AU - Caporaso, Neil

AU - Scelo, Ghislaine

AU - Zaridze, David

AU - Mukeriya, Anush

AU - Kontic, Milica

AU - Ognjanovic, Simona

AU - Lissowska, Jolanta

AU - Szołkowska, Małgorzata

AU - Swiatkowska, Beata

AU - Janout, Vladimir

AU - Holcatova, Ivana

AU - Bolca, Ciprian

AU - Savic, Milan

AU - Ognjanovic, Miodrag

AU - Bojesen, Stig Egil

AU - Wu, Xifeng

AU - Albanes, Demetrios

AU - Aldrich, Melinda C

AU - Tardon, Adonina

AU - Fernandez-Somoano, Ana

AU - Fernandez-Tardon, Guillermo

AU - Le Marchand, Loic

AU - Rennert, Gadi

AU - Chen, Chu

AU - Doherty, Jennifer

AU - Goodman, Gary

AU - Bickeböller, Heike

AU - Wichmann, H-Erich

AU - Risch, Angela

AU - Rosenberger, Albert

AU - Shen, Hongbing

AU - Dai, Juncheng

AU - Field, John K

AU - Davies, Michael

AU - Woll, Penella

AU - Teare, M Dawn

AU - Kiemeney, Lambertus A

AU - van der Heijden, Erik H F M

AU - Yuan, Jian-Min

AU - Hong, Yun-Chul

AU - Haugen, Aage

AU - Zienolddiny, Shanbeh

AU - Lam, Stephen

AU - Tsao, Ming-Sound

AU - Johansson, Mikael

AU - Grankvist, Kjell

AU - Schabath, Matthew B

AU - Andrew, Angeline

AU - Duell, Eric

AU - Melander, Olle

AU - Brunnström, Hans

AU - Lazarus, Philip

AU - Arnold, Susanne

AU - Slone, Stacey

AU - Byun, Jinyoung

AU - Kamal, Ahsan

AU - Zhu, Dakai

AU - Landi, Maria Teresa

AU - Amos, Christopher I

AU - Brennan, Paul

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - Asian Continental Ancestry Group/genetics

KW - Chromosome Mapping

KW - European Continental Ancestry Group/genetics

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease/ethnology

KW - Genotype

KW - HLA Antigens/genetics

KW - Humans

KW - Lung Neoplasms/ethnology

KW - Major Histocompatibility Complex/genetics

KW - Male

KW - Middle Aged

KW - Peptides/genetics

KW - Polymorphism, Single Nucleotide

U2 - 10.1038/s41467-018-05890-2

DO - 10.1038/s41467-018-05890-2

M3 - Journal article

C2 - 30254314

SN - 2041-1723

VL - 9

JO - Nature Communications

JF - Nature Communications

M1 - 3927

ER -

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

Abstract

Keywords

UN SDGs

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