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Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss

Author

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  • Sabrina Katrin Henne

    (University of Bonn, School of Medicine & University Hospital Bonn)

  • Rana Aldisi

    (University of Bonn)

  • Sugirthan Sivalingam

    (University of Bonn
    University of Bonn)

  • Lara Maleen Hochfeld

    (University of Bonn, School of Medicine & University Hospital Bonn)

  • Oleg Borisov

    (University of Bonn)

  • Peter Michael Krawitz

    (University of Bonn)

  • Carlo Maj

    (University of Bonn
    University Hospital of Marburg)

  • Markus Maria Nöthen

    (University of Bonn, School of Medicine & University Hospital Bonn)

  • Stefanie Heilmann-Heimbach

    (University of Bonn, School of Medicine & University Hospital Bonn)

Abstract

Male-pattern hair loss (MPHL) is common and highly heritable. While genome-wide association studies (GWAS) have generated insights into the contribution of common variants to MPHL etiology, the relevance of rare variants remains unclear. To determine the contribution of rare variants to MPHL etiology, we perform gene-based and single-variant analyses in exome-sequencing data from 72,469 male UK Biobank participants. While our population-level risk prediction suggests that rare variants make only a minor contribution to general MPHL risk, our rare variant collapsing tests identified a total of five significant gene associations. These findings provide additional evidence for previously implicated genes (EDA2R, WNT10A) and highlight novel risk genes at and beyond GWAS loci (HEPH, CEPT1, EIF3F). Furthermore, MPHL-associated genes are enriched for genes considered causal for monogenic trichoses. Together, our findings broaden the MPHL-associated allelic spectrum and provide insights into MPHL pathobiology and a shared basis with monogenic hair loss disorders.

Suggested Citation

  • Sabrina Katrin Henne & Rana Aldisi & Sugirthan Sivalingam & Lara Maleen Hochfeld & Oleg Borisov & Peter Michael Krawitz & Carlo Maj & Markus Maria Nöthen & Stefanie Heilmann-Heimbach, 2023. "Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41186-w
    DOI: 10.1038/s41467-023-41186-w
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    References listed on IDEAS

    as
    1. Stefanie Heilmann-Heimbach & Christine Herold & Lara M. Hochfeld & Axel M. Hillmer & Dale R. Nyholt & Julian Hecker & Asif Javed & Elaine G. Y. Chew & Sonali Pechlivanis & Dmitriy Drichel & Xiu Ting H, 2017. "Meta-analysis identifies novel risk loci and yields systematic insights into the biology of male-pattern baldness," Nature Communications, Nature, vol. 8(1), pages 1-8, April.
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    3. 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.
    4. Kaustubh Adhikari & Tania Fontanil & Santiago Cal & Javier Mendoza-Revilla & Macarena Fuentes-Guajardo & Juan-Camilo Chacón-Duque & Farah Al-Saadi & Jeanette A. Johansson & Mirsha Quinto-Sanchez & Vic, 2016. "A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features," Nature Communications, Nature, vol. 7(1), pages 1-12, April.
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