A new study has discovered rare genetic variants linked to male pattern hair loss, including two that have never been discovered before. In addition to deepening our understanding of the disease, these findings may pave the way for personalized treatments.
Androgenic alopecia, or male pattern hair loss (MPHL), affects 30 to 50 percent of men over the age of 50. About 80% of MPHL cases are caused by genetic factors. Worldwide, research into the genetic basis of MPHL has focused on common variants, identifying more than 350 genetic loci, including the maternally inherited X-chromosome-linked androgen receptor gene.
Now, new research led by the University Hospital Bonn in Germany has not only analyzed common genetic variants, but also included rare genetic variants to gain a deeper understanding of the disease.
"Such analyzes are more challenging because they require large cohorts and the genetic sequence must be obtained base by base through methods such as genome or exome sequencing of affected individuals," said Sabrina Henne, the study's lead author.
This is tantamount to finding a needle in a haystack, because statistically speaking only a few people - or even just one person - carry a specific variant.
"We therefore used a gene-based analysis approach, first classifying variants according to the gene in which they reside," said Stefanie Heilmann-Heimback, corresponding author of the study.
Researchers obtained data from 72,469 men aged 39 to 82 years from the UK Biobank and used sequencing nuclear association testing (SKAT) and GenRisk (GenRisk is an open source python package that provides a framework for modeling the impact of rare functional genetic variants) to study variants with an incidence of less than 1%.
They found rare genetic variants in five genes: EDA2R, WNT10A, HEPH, CEPT1 and EIF3F. EDA2R and WNT10A had been considered candidate genes based on analyzes of common variants, but the findings confirmed that they also play a role as rare variants.
"Our study provides further evidence of the role of these two genes, and by both common and rare variants," Heilmann-Heimbach said.
Likewise, HEPH is located in a genetic region near EDA2R and the androgen receptor, which has been most closely associated with hair loss in past genetic association studies.
"However, HEPH itself was never considered a candidate gene," Henne said. "Our study shows that HEPH may also play a role in hair loss. The genes CEPT1 and EIF3F are located in a genetic region that has not been associated with male pattern baldness. Therefore, they are completely new candidate genes and we hypothesize that rare variants in these genes contribute to genetic susceptibility. Given their previous roles in hair development and growth, HEPH, CEPT1 and EIF3F are very credible new candidate genes."
The findings also suggest that genes known to cause rare genetic disorders that affect the skin and hair, such as ectodermal dysplasia, may also play a role in the development of MPHL.
Further research is needed to investigate the interaction between rare and common genetic variants in MPHL and how rare variants contribute to the development of the disease. The researchers hope that the additional information provided by their study will lead to better personalized treatment strategies for men with hereditary alopecia.
The research was published in the journal Nature Communications.