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

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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Science Q
Acceso en línea:	https://doaj.org/article/09d1442134c6443f915b29ea5ec5ae4d
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spelling	oai:doaj.org-article:09d1442134c6443f915b29ea5ec5ae4d2021-12-02T17:32:01ZFine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity10.1038/s41467-018-05890-22041-1723https://doaj.org/article/09d1442134c6443f915b29ea5ec5ae4d2018-09-01T00:00:00Zhttps://doi.org/10.1038/s41467-018-05890-2https://doaj.org/toc/2041-1723Abstract 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-B0801 peptide binding groove and an independent HLA-DQB106 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB10401 and HLA-DRB10701; 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.Aida Ferreiro-IglesiasCorina LesseurJames McKayRayjean J. HungYounghun HanXuchen ZongDavid ChristianiMattias JohanssonXiangjun XiaoYafang LiDavid C. QianXuemei JiGeoffrey LiuNeil CaporasoGhislaine SceloDavid ZaridzeAnush MukeriyaMilica KonticSimona OgnjanovicJolanta LissowskaMałgorzata SzołkowskaBeata SwiatkowskaVladimir JanoutIvana HolcatovaCiprian BolcaMilan SavicMiodrag OgnjanovicStig Egil BojesenXifeng WuDemetrios AlbanesMelinda C. AldrichAdonina TardonAna Fernandez-SomoanoGuillermo Fernandez-TardonLoic Le MarchandGadi RennertChu ChenJennifer DohertyGary GoodmanHeike BickeböllerH-Erich WichmannAngela RischAlbert RosenbergerHongbing ShenJuncheng DaiJohn K. FieldMichael DaviesPenella WollM. Dawn TeareLambertus A. KiemeneyErik H. F. M. van der HeijdenJian-Min YuanYun-Chul HongAage HaugenShanbeh ZienolddinyStephen LamMing-Sound TsaoMikael JohanssonKjell GrankvistMatthew B. SchabathAngeline AndrewEric DuellOlle MelanderHans BrunnströmPhilip LazarusSusanne ArnoldStacey SloneJinyoung ByunAhsan KamalDakai ZhuMaria Teresa LandiChristopher I. AmosPaul BrennanNature PortfolioarticleScienceQENNature Communications, Vol 9, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Science Q
spellingShingle	Science Q 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 Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
description	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-B0801 peptide binding groove and an independent HLA-DQB106 loci group. In Asians, associations are driven by two independent HLA allele sets that both increase risk in HLA-DQB10401 and HLA-DRB10701; 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.
format	article
author	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
author_facet	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
author_sort	Aida Ferreiro-Iglesias
title	Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
title_short	Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
title_full	Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
title_fullStr	Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
title_full_unstemmed	Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity
title_sort	fine mapping of mhc region in lung cancer highlights independent susceptibility loci by ethnicity
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/09d1442134c6443f915b29ea5ec5ae4d
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Fine mapping of MHC region in lung cancer highlights independent susceptibility loci by ethnicity

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