| Title: | Large-Scale Plasma Proteomics and Genetic Integration Uncover Novel Biological Pathways in Male Pattern Baldness |
| Journal: | International Journal of Molecular Sciences |
| Published: | 22 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41752186/ |
| DOI: | https://doi.org/10.3390/ijms27042052 |
| URL: | http://dx.doi.org/10.3390/ijms27042052 |
Publication 17680
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Male pattern baldness (MPB) is a highly prevalent condition with a complex, poorly understood molecular basis that limits therapeutic innovation. This study aimed to bridge the gap between statistical genetic associations and biological function by identifying and prioritizing causal proteins and pathways involved in MPB. Using data from 24,069 men in the UK Biobank, we performed a proteome-wide association study of 2911 plasma proteins with self-reported MPB severity via multivariable ordinal logistic regression, adjusting for age, Body Mass Index (BMI), ethnicity, lifestyle, socioeconomic factors, and testosterone levels. Significant proteins underwent pathway enrichment analysis. Genetic integration included MAGMA for gene-level aggregation and tissue prioritization, transcriptome-wide association studies (TWAS) with GTEx models, conditional fine-mapping, and validation in an independent scalp biopsy transcriptomics dataset (GSE90594). Druggability and pleiotropy were evaluated using databases and phenome-wide association studies. Forty-seven proteins were significantly associated with MPB severity, enriched in pathways involving epidermis development, hair cycle regulation, and cell adhesion. Multi-omic integration prioritized five independent candidate genes: CD38, FGF5, TACSTD2, DPEP1, and PLB1. Transcriptomic validation confirmed differential expression in balding scalp for CD38 (upregulated) and TACSTD2, PLB1 (downregulated). CD38 was identified as druggable with low pleiotropic risks. This study elucidates the molecular architecture of MPB, revealing novel biological pathways beyond canonical androgen signaling. By prioritizing promising non-hormonal targets like CD38, our findings provide a robust, evidence-based framework to guide the development of future therapeutic interventions for this common condition.</p>
11 Keywords
- Adult
- Alopecia
- Blood Proteins
- Genome-Wide Association Study
- Humans
- Male
- Middle Aged
- Proteome
- Proteomics
- Signal Transduction
- Transcriptome
8 Authors
- Lingfeng Pan
- Caihong Li
- Philipp Moog
- Samuel Knoedler
- Haydar Kükrek
- Ulf Dornseifer
- Hans-Günther Machens
- Jun Jiang
1 Application
| Application ID | Title |
|---|---|
| 687300 | Integrating Genetics, Omics Data, Epidemiology, and UK Biobank Data to Enhance Understanding of Skin Lesion Disease Etiology |
Enabling scientific discoveries that improve human health