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A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma

Author

Listed:
  • Mathias Seviiri

    (QIMR Berghofer Medical Research Institute
    Queensland University of Technology
    Queensland University of Technology)

  • Matthew H. Law

    (QIMR Berghofer Medical Research Institute
    Queensland University of Technology)

  • Jue-Sheng Ong

    (QIMR Berghofer Medical Research Institute)

  • Puya Gharahkhani

    (QIMR Berghofer Medical Research Institute)

  • Pierre Fontanillas

    (23andMe, Inc)

  • Catherine M. Olsen

    (QIMR Berghofer Medical Research Institute
    University of Queensland)

  • David C. Whiteman

    (University of Queensland)

  • Stuart MacGregor

    (QIMR Berghofer Medical Research Institute
    Queensland University of Technology)

Abstract

Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-35345-8
    DOI: 10.1038/s41467-022-35345-8
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    as
    1. 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.
    2. Vincent Plagnol & Joanna M M Howson & Deborah J Smyth & Neil Walker & Jason P Hafler & Chris Wallace & Helen Stevens & Laura Jackson & Matthew J Simmonds & Type 1 Diabetes Genetics Consortium & Polly , 2011. "Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases," PLOS Genetics, Public Library of Science, vol. 7(8), pages 1-9, August.
    3. Harvind S. Chahal & Yuan Lin & Katherine J. Ransohoff & David A. Hinds & Wenting Wu & Hong-Ji Dai & Abrar A. Qureshi & Wen-Qing Li & Peter Kraft & Jean Y. Tang & Jiali Han & Kavita Y. Sarin, 2016. "Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma," Nature Communications, Nature, vol. 7(1), pages 1-8, November.
    4. Kun-Ju Zhu & Yong-Mei Lv & Xian-Yong Yin & Zai-Xing Wang & Liang-Dan Sun & Su-Min He & Hui Cheng & Da-Yan Hu & Zheng Zhang & Yang Li & Xian-Bo Zuo & You-Wen Zhou & Sen Yang & Xing Fan & Xue-Jun Zhang , 2011. "Psoriasis Regression Analysis of MHC Loci Identifies Shared Genetic Variants with Vitiligo," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-7, November.
    5. Michael D. Morgan & Erola Pairo-Castineira & Konrad Rawlik & Oriol Canela-Xandri & Jonathan Rees & David Sims & Albert Tenesa & Ian J. Jackson, 2018. "Genome-wide study of hair colour in UK Biobank explains most of the SNP heritability," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
    6. Yeda Wu & Enda M. Byrne & Zhili Zheng & Kathryn E. Kemper & Loic Yengo & Andrew J. Mallett & Jian Yang & Peter M. Visscher & Naomi R. Wray, 2019. "Genome-wide association study of medication-use and associated disease in the UK Biobank," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    7. 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.
    8. Aysu Okbay & Jonathan P. Beauchamp & Mark Alan Fontana & James J. Lee & Tune H. Pers & Cornelius A. Rietveld & Patrick Turley & Guo-Bo Chen & Valur Emilsson & S. Fleur W. Meddens & Sven Oskarsson & Jo, 2016. "Genome-wide association study identifies 74 loci associated with educational attainment," Nature, Nature, vol. 533(7604), pages 539-542, May.
    9. Harvind S. Chahal & Wenting Wu & Katherine J. Ransohoff & Lingyao Yang & Haley Hedlin & Manisha Desai & Yuan Lin & Hong-Ji Dai & Abrar A. Qureshi & Wen-Qing Li & Peter Kraft & David A. Hinds & Jean Y., 2016. "Genome-wide association study identifies 14 novel risk alleles associated with basal cell carcinoma," Nature Communications, Nature, vol. 7(1), pages 1-10, November.
    10. Daniel Taliun & Daniel N. Harris & Michael D. Kessler & Jedidiah Carlson & Zachary A. Szpiech & Raul Torres & Sarah A. Gagliano Taliun & André Corvelo & Stephanie M. Gogarten & Hyun Min Kang & Achille, 2021. "Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program," Nature, Nature, vol. 590(7845), pages 290-299, February.
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