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 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.

Application of multi-omics techniques to androgenetic alopecia: Current status and perspectives

“…Sabrina et al conducted gene-based and single-variant analyses of exome sequencing data from a large cohort of 72,469 men to investigate the contribution of rare genetic variants to the development of MPHL, and identified five significant genetic associations and provided further support for previously implicated genes such as EDA2R and WNT10A while also discovering new risk genes such as HEPH , CEPT1 , and EIF3F. Additionally, genes related to MPHL are now considered to be pathogenic genes within a single gene triad, expanding the spectrum of alleles associated with MPHL and offering insights into its pathologic biology [35] . GWAS have also indicated the potential involvement of WNT signaling in AGA [36] .…”