IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39136-7.html
   My bibliography  Save this article

Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis

Author

Listed:
  • Go Sato

    (Osaka University Graduate School of Medicine
    Osaka University)

  • Yuya Shirai

    (Osaka University Graduate School of Medicine
    Osaka University Graduate School of Medicine
    Osaka University)

  • Shinichi Namba

    (Osaka University Graduate School of Medicine)

  • Ryuya Edahiro

    (Osaka University Graduate School of Medicine
    Osaka University Graduate School of Medicine)

  • Kyuto Sonehara

    (Osaka University Graduate School of Medicine
    RIKEN Center for Integrative Medical Sciences
    the University of Tokyo)

  • Tsuyoshi Hata

    (Osaka University)

  • Mamoru Uemura

    (Osaka University)

  • Koichi Matsuda

    (the University of Tokyo)

  • Yuichiro Doki

    (Osaka University)

  • Hidetoshi Eguchi

    (Osaka University)

  • Yukinori Okada

    (Osaka University Graduate School of Medicine
    Osaka University
    RIKEN Center for Integrative Medical Sciences
    the University of Tokyo)

Abstract

Integrating genomic data of multiple cancers allows de novo cancer grouping and elucidating the shared genetic basis across cancers. Here, we conduct the pan-cancer and cross-population genome-wide association study (GWAS) meta-analysis and replication studies on 13 cancers including 250,015 East Asians (Biobank Japan) and 377,441 Europeans (UK Biobank). We identify ten cancer risk variants including five pleiotropic associations (e.g., rs2076295 at DSP on 6p24 associated with lung cancer and rs2525548 at TRIM4 on 7q22 nominally associated with six cancers). Quantifying shared heritability among the cancers detects positive genetic correlations between breast and prostate cancer across populations. Common genetic components increase the statistical power, and the large-scale meta-analysis of 277,896 breast/prostate cancer cases and 901,858 controls identifies 91 newly genome-wide significant loci. Enrichment analysis of pathways and cell types reveals shared genetic backgrounds across said cancers. Focusing on genetically correlated cancers can contribute to enhancing our insights into carcinogenesis.

Suggested Citation

  • Go Sato & Yuya Shirai & Shinichi Namba & Ryuya Edahiro & Kyuto Sonehara & Tsuyoshi Hata & Mamoru Uemura & Koichi Matsuda & Yuichiro Doki & Hidetoshi Eguchi & Yukinori Okada, 2023. "Pan-cancer and cross-population genome-wide association studies dissect shared genetic backgrounds underlying carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39136-7
    DOI: 10.1038/s41467-023-39136-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39136-7
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39136-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Corina Lesseur & Aida Ferreiro-Iglesias & James D McKay & Yohan Bossé & Mattias Johansson & Valerie Gaborieau & Maria Teresa Landi & David C Christiani & Neil C Caporaso & Stig E Bojesen & Christopher, 2021. "Genome-wide association meta-analysis identifies pleiotropic risk loci for aerodigestive squamous cell cancers," PLOS Genetics, Public Library of Science, vol. 17(3), pages 1-19, March.
    2. Kyriaki Michailidou & Sara Lindström & Joe Dennis & Jonathan Beesley & Shirley Hui & Siddhartha Kar & Audrey Lemaçon & Penny Soucy & Dylan Glubb & Asha Rostamianfar & Manjeet K. Bolla & Qin Wang & Jon, 2017. "Association analysis identifies 65 new breast cancer risk loci," Nature, Nature, vol. 551(7678), pages 92-94, November.
    3. David Lamparter & Daniel Marbach & Rico Rueedi & Zoltán Kutalik & Sven Bergmann, 2016. "Fast and Rigorous Computation of Gene and Pathway Scores from SNP-Based Summary Statistics," PLOS Computational Biology, Public Library of Science, vol. 12(1), pages 1-20, January.
    4. Xia Jiang & Hilary K. Finucane & Fredrick R. Schumacher & Stephanie L. Schmit & Jonathan P. Tyrer & Younghun Han & Kyriaki Michailidou & Corina Lesseur & Karoline B. Kuchenbaecker & Joe Dennis & David, 2019. "Publisher Correction: Shared heritability and functional enrichment across six solid cancers," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    5. Xia Jiang & Hilary K. Finucane & Fredrick R. Schumacher & Stephanie L. Schmit & Jonathan P. Tyrer & Younghun Han & Kyriaki Michailidou & Corina Lesseur & Karoline B. Kuchenbaecker & Joe Dennis & David, 2019. "Shared heritability and functional enrichment across six solid cancers," Nature Communications, Nature, vol. 10(1), pages 1-23, December.
    6. Naim Panjwani & Fan Wang & Scott Mastromatteo & Allen Bao & Cheng Wang & Gengming He & Jiafen Gong & Johanna M Rommens & Lei Sun & Lisa J Strug, 2020. "LocusFocus: Web-based colocalization for the annotation and functional follow-up of GWAS," PLOS Computational Biology, Public Library of Science, vol. 16(10), pages 1-8, October.
    7. Sara R. Rashkin & Rebecca E. Graff & Linda Kachuri & Khanh K. Thai & Stacey E. Alexeeff & Maruta A. Blatchins & Taylor B. Cavazos & Douglas A. Corley & Nima C. Emami & Joshua D. Hoffman & Eric Jorgens, 2020. "Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    8. Masato Akiyama & Kazuyoshi Ishigaki & Saori Sakaue & Yukihide Momozawa & Momoko Horikoshi & Makoto Hirata & Koichi Matsuda & Shiro Ikegawa & Atsushi Takahashi & Masahiro Kanai & Sadao Suzuki & Daisuke, 2019. "Characterizing rare and low-frequency height-associated variants in the Japanese population," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    9. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    10. Kyoko Watanabe & Erdogan Taskesen & Arjen Bochoven & Danielle Posthuma, 2017. "Functional mapping and annotation of genetic associations with FUMA," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    11. Yukinori Okada & Yukihide Momozawa & Saori Sakaue & Masahiro Kanai & Kazuyoshi Ishigaki & Masato Akiyama & Toshihiro Kishikawa & Yasumichi Arai & Takashi Sasaki & Kenjiro Kosaki & Makoto Suematsu & Ko, 2018. "Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Yaohua Yang & Yaxin Chen & Shuai Xu & Xingyi Guo & Guochong Jia & Jie Ping & Xiang Shu & Tianying Zhao & Fangcheng Yuan & Gang Wang & Yufang Xie & Hang Ci & Hongmo Liu & Yawen Qi & Yongjun Liu & Dan L, 2024. "Integrating muti-omics data to identify tissue-specific DNA methylation biomarkers for cancer risk," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Hui Chen & Zeyang Wang & Lihai Gong & Qixuan Wang & Wenyan Chen & Jia Wang & Xuelian Ma & Ruofan Ding & Xing Li & Xudong Zou & Mireya Plass & Cheng Lian & Ting Ni & Gong-Hong Wei & Wei Li & Lin Deng &, 2024. "A distinct class of pan-cancer susceptibility genes revealed by an alternative polyadenylation transcriptome-wide association study," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Gengjie Jia & Xue Zhong & Hae Kyung Im & Nathan Schoettler & Milton Pividori & D. Kyle Hogarth & Anne I. Sperling & Steven R. White & Edward T. Naureckas & Christopher S. Lyttle & Chikashi Terao & Yoi, 2022. "Discerning asthma endotypes through comorbidity mapping," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    3. Kenichi Yamamoto & Kyuto Sonehara & Shinichi Namba & Takahiro Konuma & Hironori Masuko & Satoru Miyawaki & Yoichiro Kamatani & Nobuyuki Hizawa & Keiichi Ozono & Loic Yengo & Yukinori Okada, 2023. "Genetic footprints of assortative mating in the Japanese population," Nature Human Behaviour, Nature, vol. 7(1), pages 65-73, January.
    4. Kenichi Yamamoto & Shinichi Namba & Kyuto Sonehara & Ken Suzuki & Saori Sakaue & Niall P. Cooke & Shinichi Higashiue & Shuzo Kobayashi & Hisaaki Afuso & Kosho Matsuura & Yojiro Mitsumoto & Yasuhiko Fu, 2024. "Genetic legacy of ancient hunter-gatherer Jomon in Japanese populations," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Natalie DeForest & Yuqi Wang & Zhiyi Zhu & Jacqueline S. Dron & Ryan Koesterer & Pradeep Natarajan & Jason Flannick & Tiffany Amariuta & Gina M. Peloso & Amit R. Majithia, 2024. "Genome-wide discovery and integrative genomic characterization of insulin resistance loci using serum triglycerides to HDL-cholesterol ratio as a proxy," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    6. Shahram Bahrami & Kaja Nordengen & Jaroslav Rokicki & Alexey A. Shadrin & Zillur Rahman & Olav B. Smeland & Piotr P. Jaholkowski & Nadine Parker & Pravesh Parekh & Kevin S. O’Connell & Torbjørn Elvsås, 2024. "The genetic landscape of basal ganglia and implications for common brain disorders," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    8. Zhen Qiao & Julia Sidorenko & Joana A. Revez & Angli Xue & Xueling Lu & Katri Pärna & Harold Snieder & Peter M. Visscher & Naomi R. Wray & Loic Yengo, 2023. "Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Fasil Tekola-Ayele & Xuehuo Zeng & Suvo Chatterjee & Marion Ouidir & Corina Lesseur & Ke Hao & Jia Chen & Markos Tesfaye & Carmen J. Marsit & Tsegaselassie Workalemahu & Ronald Wapner, 2022. "Placental multi-omics integration identifies candidate functional genes for birthweight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Xingjie Hao & Zhonghe Shao & Ning Zhang & Minghui Jiang & Xi Cao & Si Li & Yunlong Guan & Chaolong Wang, 2023. "Integrative genome-wide analyses identify novel loci associated with kidney stones and provide insights into its genetic architecture," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    11. Bingxin Zhao & Yujue Li & Zirui Fan & Zhenyi Wu & Juan Shu & Xiaochen Yang & Yilin Yang & Xifeng Wang & Bingxuan Li & Xiyao Wang & Carlos Copana & Yue Yang & Jinjie Lin & Yun Li & Jason L. Stein & Joa, 2024. "Eye-brain connections revealed by multimodal retinal and brain imaging genetics," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    12. Isabelle Austin-Zimmerman & Daniel F. Levey & Olga Giannakopoulou & Joseph D. Deak & Marco Galimberti & Keyrun Adhikari & Hang Zhou & Spiros Denaxas & Haritz Irizar & Karoline Kuchenbaecker & Andrew M, 2023. "Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    13. Peter Zhukovsky & Earvin S. Tio & Gillian Coughlan & David A. Bennett & Yanling Wang & Timothy J. Hohman & Diego A. Pizzagalli & Benoit H. Mulsant & Aristotle N. Voineskos & Daniel Felsky, 2024. "Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    14. Wenhan Chen & Yang Wu & Zhili Zheng & Ting Qi & Peter M. Visscher & Zhihong Zhu & Jian Yang, 2021. "Improved analyses of GWAS summary statistics by reducing data heterogeneity and errors," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    15. Keira J A Johnston & Joey Ward & Pradipta R Ray & Mark J Adams & Andrew M McIntosh & Blair H Smith & Rona J Strawbridge & Theodore J Price & Daniel J Smith & Barbara I Nicholl & Mark E S Bailey, 2021. "Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank," PLOS Genetics, Public Library of Science, vol. 17(4), pages 1-27, April.
    16. Xiaofeng Zhu & Yihe Yang & Noah Lorincz-Comi & Gen Li & Amy R. Bentley & Paul S. de Vries & Michael Brown & Alanna C. Morrison & Charles N. Rotimi & W. James Gauderman & Dabeeru C. Rao & Hugues Aschar, 2024. "An approach to identify gene-environment interactions and reveal new biological insight in complex traits," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    17. Sophie A. Riesmeijer & Zoha Kamali & Michael Ng & Dmitriy Drichel & Bram Piersma & Kerstin Becker & Thomas B. Layton & Jagdeep Nanchahal & Michael Nothnagel & Ahmad Vaez & Hans Christian Hennies & Pau, 2024. "A genome-wide association meta-analysis implicates Hedgehog and Notch signaling in Dupuytren’s disease," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    18. Fotios Koskeridis & Evangelos Evangelou & Saredo Said & Joseph J. Boyle & Paul Elliott & Abbas Dehghan & Ioanna Tzoulaki, 2022. "Pleiotropic genetic architecture and novel loci for C-reactive protein levels," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    19. Jakub Kopal & Kuldeep Kumar & Kimia Shafighi & Karin Saltoun & Claudia Modenato & Clara A. Moreau & Guillaume Huguet & Martineau Jean-Louis & Charles-Olivier Martin & Zohra Saci & Nadine Younis & Elis, 2024. "Using rare genetic mutations to revisit structural brain asymmetry," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    20. Zhiqiang Sha & Dick Schijven & Amaia Carrion-Castillo & Marc Joliot & Bernard Mazoyer & Simon E. Fisher & Fabrice Crivello & Clyde Francks, 2021. "The genetic architecture of structural left–right asymmetry of the human brain," Nature Human Behaviour, Nature, vol. 5(9), pages 1226-1239, September.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39136-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.