A new study has identified rare genetic variants associated with male pattern hair loss, including two that haven’t been identified before. In addition to increasing our understanding of the condition, the findings may pave the way for personalized therapies.
Androgenetic alopecia, or male pattern hair loss (MPHL), affects between 30% and 50% of men by age 50. About 80% of cases of MPHL are caused by genetic factors. Worldwide, studies into the genetics underlying MPHL have focused on common variants, identifying more than 350 gene loci, including the X-chromosome-linked androgen receptor gene passed on by the mother.
Now, new research led by the University Hospital of Bonn, Germany, has looked beyond analyzing common genetic variants to include rarer ones in an effort to gain an increased understanding of the condition.
“Such analyses are more challenging as they require large cohorts, and the genetic sequences must be captured base by base, e.g., through genome or exome sequencing of affected individuals,” said Sabrina Henne, lead author of the study.
It’s akin to finding a needle in a haystack as, statistically speaking, only a few people – or even just one – carry the specific variants.
“That is why we apply gene-based analyses that first collapse variants on the basis of the genes in which they are located,” said Stefanie Heilmann-Heimback, the study’s corresponding author.
Obtaining data from the UK Biobank relating to 72,469 men aged 39 to 82 years, the researchers used the sequencing kernel association test (SKAT), a method of testing for rare genetic variants in a region relating to an individual’s observable traits (phenotype), and GenRisk, an open source python package which provides a framework to model the effects of rare functional genetic variants, to look at variants that occur in less than 1% of the population.
They found rare genetic variants in five genes: EDA2R, WNT10A, HEPH, CEPT1, and EIF3F. EDA2R and WNT10A were already considered candidate genes based on analyses of common variants, but the findings confirmed that they also played a role as rare variants.
“Our study provides further evidence that these two genes play a role and that this occurs through both common and rare variants,” Heilmann-Heimbach said.
Similarly, HEPH is located in a genetic region near EDA2R and the androgen receptor, the region that has been most strongly associated with hair loss in past genetic association studies.
“However, HEPH itself has never been considered as a candidate gene,” said Henne. “Our study suggests that it may also play a role. The genes CEPT1 and EIF3F are located in genetic regions that have not yet been associated with male pattern hair loss. They are thus entirely new candidate genes, and we hypothesize that rare variants within these genes contribute to the genetic predisposition. HEPH, CEPT1, and EIF3F represent highly plausible new candidate genes, given their previously described role in hair development and growth.”
The findings also suggest that genes known to cause rare inherited diseases affecting the skin and hair, such as ectodermal dysplasia, may also play a role in the development of MPHL.
Further studies are needed to investigate the interactions between rare and common genetic variants of MPHL and how rare variants contribute to the development of the condition. The researchers hope that the additional information their research provides will lead to improved, personalized treatment strategies for men suffering from inherited hair loss.
The study was published in the journal Nature Communications.
Source: Universitätsklinikum Bonn
