IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-06649-5.html
   My bibliography  Save this article

Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Author

Listed:
  • David L. Duffy

    (QIMR Berghofer Medical Research Institute)

  • Gu Zhu

    (QIMR Berghofer Medical Research Institute)

  • Xin Li

    (Indiana University)

  • Marianna Sanna

    (St Thomas Hospital Campus, Kings College)

  • Mark M. Iles

    (Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds)

  • Leonie C. Jacobs

    (University Medical Centre Rotterdam)

  • David M. Evans

    (University of Bristol
    University of Queensland Diamantina Institute, Translational Research Institute)

  • Seyhan Yazar

    (University of Western Australia and the Lions Eye Institute)

  • Jonathan Beesley

    (QIMR Berghofer Medical Research Institute)

  • Matthew H. Law

    (QIMR Berghofer Medical Research Institute)

  • Peter Kraft

    (Harvard T.H. Chan School of Public Health)

  • Alessia Visconti

    (St Thomas Hospital Campus, Kings College)

  • John C. Taylor

    (Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds)

  • Fan Liu

    (University Medical Centre Rotterdam)

  • Margaret J. Wright

    (QIMR Berghofer Medical Research Institute)

  • Anjali K. Henders

    (QIMR Berghofer Medical Research Institute
    Institute for Molecular Bioscience, The University of Queensland)

  • Lisa Bowdler

    (QIMR Berghofer Medical Research Institute)

  • Dan Glass

    (St Thomas Hospital Campus, Kings College)

  • M. Arfan Ikram

    (Erasmus MC)

  • André G. Uitterlinden

    (Erasmus MC
    Erasmus MC)

  • Pamela A. Madden

    (Washington University School of Medicine)

  • Andrew C. Heath

    (Washington University School of Medicine)

  • Elliot C. Nelson

    (Washington University School of Medicine)

  • Adele C. Green

    (QIMR Berghofer Medical Research Institute
    CRUK Manchester Institute, University of Manchester)

  • Stephen Chanock

    (National Cancer Institute)

  • Jennifer H. Barrett

    (Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds)

  • Matthew A. Brown

    (University of Queensland Diamantina Institute, Translational Research Institute)

  • Nicholas K. Hayward

    (QIMR Berghofer Medical Research Institute)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute)

  • Richard A. Sturm

    (University of Queensland Diamantina Institute, Translational Research Institute)

  • Alex W. Hewitt

    (University of Western Australia and the Lions Eye Institute)

  • Manfred Kayser

    (University Medical Centre Rotterdam)

  • David J. Hunter

    (Harvard T.H. Chan School of Public Health)

  • Julia A. Newton Bishop

    (Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds)

  • Timothy D. Spector

    (St Thomas Hospital Campus, Kings College)

  • Grant W. Montgomery

    (QIMR Berghofer Medical Research Institute
    Institute for Molecular Bioscience, The University of Queensland)

  • David A. Mackey

    (University of Western Australia and the Lions Eye Institute)

  • George Davey Smith

    (University of Bristol)

  • Tamar E. Nijsten

    (University Medical Centre Rotterdam)

  • D. Timothy Bishop

    (Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds)

  • Veronique Bataille

    (St Thomas Hospital Campus, Kings College)

  • Mario Falchi

    (St Thomas Hospital Campus, Kings College)

  • Jiali Han

    (Indiana University)

  • Nicholas G. Martin

    (QIMR Berghofer Medical Research Institute)

Abstract

The total number of acquired melanocytic nevi on the skin is strongly correlated with melanoma risk. Here we report a meta-analysis of 11 nevus GWAS from Australia, Netherlands, UK, and USA comprising 52,506 individuals. We confirm known loci including MTAP, PLA2G6, and IRF4, and detect novel SNPs in KITLG and a region of 9q32. In a bivariate analysis combining the nevus results with a recent melanoma GWAS meta-analysis (12,874 cases, 23,203 controls), SNPs near GPRC5A, CYP1B1, PPARGC1B, HDAC4, FAM208B, DOCK8, and SYNE2 reached global significance, and other loci, including MIR146A and OBFC1, reached a suggestive level. Overall, we conclude that most nevus genes affect melanoma risk (KITLG an exception), while many melanoma risk loci do not alter nevus count. For example, variants in TERC and OBFC1 affect both traits, but other telomere length maintenance genes seem to affect melanoma risk only. Our findings implicate multiple pathways in nevogenesis.

Suggested Citation

  • David L. Duffy & Gu Zhu & Xin Li & Marianna Sanna & Mark M. Iles & Leonie C. Jacobs & David M. Evans & Seyhan Yazar & Jonathan Beesley & Matthew H. Law & Peter Kraft & Alessia Visconti & John C. Taylo, 2018. "Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06649-5
    DOI: 10.1038/s41467-018-06649-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-06649-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-06649-5?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
    ---><---

    Citations

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


    Cited by:

    1. Jue-Sheng Ong & Mathias Seviiri & Jean Claude Dusingize & Yeda Wu & Xikun Han & Jianxin Shi & Catherine M. Olsen & Rachel E. Neale & John F. Thompson & Robyn P. M. Saw & Kerwin F. Shannon & Graham J. , 2023. "Uncovering the complex relationship between balding, testosterone and skin cancers in men," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    2. Rishi Kumar Jaiswal & Kai-Hang Lei & Megan Chastain & Yuan Wang & Olga Shiva & Shan Li & Zhongsheng You & Peter Chi & Weihang Chai, 2023. "CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    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:9:y:2018:i:1:d:10.1038_s41467-018-06649-5. 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.

    We have no bibliographic references for this item. You can help adding them by using 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.