Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss
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 MPH...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-41186-w |
| _version_ | 1797557823974932480 |
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| author | Sabrina Katrin Henne Rana Aldisi Sugirthan Sivalingam Lara Maleen Hochfeld Oleg Borisov Peter Michael Krawitz Carlo Maj Markus Maria Nöthen Stefanie Heilmann-Heimbach |
| author_facet | Sabrina Katrin Henne Rana Aldisi Sugirthan Sivalingam Lara Maleen Hochfeld Oleg Borisov Peter Michael Krawitz Carlo Maj Markus Maria Nöthen Stefanie Heilmann-Heimbach |
| author_sort | Sabrina Katrin Henne |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:22:41Z |
| format | Article |
| id | doaj.art-a171b6aa33ba46fa9e50d5a3280cd103 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:22:41Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-a171b6aa33ba46fa9e50d5a3280cd1032023-11-20T10:18:18ZengNature PortfolioNature Communications2041-17232023-09-0114111310.1038/s41467-023-41186-wAnalysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair lossSabrina Katrin Henne0Rana Aldisi1Sugirthan Sivalingam2Lara Maleen Hochfeld3Oleg Borisov4Peter Michael Krawitz5Carlo Maj6Markus Maria Nöthen7Stefanie Heilmann-Heimbach8Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute for Genomic Statistics and Bioinformatics, University of BonnInstitute for Genomic Statistics and Bioinformatics, University of BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute for Genomic Statistics and Bioinformatics, University of BonnInstitute for Genomic Statistics and Bioinformatics, University of BonnInstitute for Genomic Statistics and Bioinformatics, University of BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnInstitute of Human Genetics, University of Bonn, School of Medicine & University Hospital BonnAbstract 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.https://doi.org/10.1038/s41467-023-41186-w |
| spellingShingle | Sabrina Katrin Henne Rana Aldisi Sugirthan Sivalingam Lara Maleen Hochfeld Oleg Borisov Peter Michael Krawitz Carlo Maj Markus Maria Nöthen Stefanie Heilmann-Heimbach Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss Nature Communications |
| title | Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss |
| title_full | Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss |
| title_fullStr | Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss |
| title_full_unstemmed | Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss |
| title_short | Analysis of 72,469 UK Biobank exomes links rare variants to male-pattern hair loss |
| title_sort | analysis of 72 469 uk biobank exomes links rare variants to male pattern hair loss |
| url | https://doi.org/10.1038/s41467-023-41186-w |
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