New Rare Gene Discovery Sheds Light on Male Baldness

A recent research endeavor has pinpointed uncommon genetic variations linked to male pattern baldness, including two previously unknown ones. Beyond expanding our comprehension of this condition, these discoveries hold the potential to open the door to personalized treatment approaches.

Androgenetic alopecia, commonly known as male pattern hair loss (MPHL), impacts approximately 30% to 50% of men by the time they reach the age of 50. Genetic factors contribute to about 80% of MPHL cases.

Exploring Common Variations in MPHL

On a global scale, investigations into the genetic basis of MPHL have primarily concentrated on common genetic variations, revealing over 350 gene locations, which include the X-chromosome-linked androgen receptor gene inherited from the mother.

Presently, a fresh investigation led by the University Hospital of Bonn, Germany, has expanded its scope beyond the examination of common genetic variations, incorporating the study of less common ones with the aim of deepening our comprehension of this condition.

The Complexities of Genetic Investigations

Sabrina Henne, the study’s lead author, pointed out the intricacies of such analyses, stating, “These investigations are more demanding, as they necessitate sizable study groups and the meticulous sequencing of genetic sequences, often performed through comprehensive methods like genome or exome sequencing on individuals affected by the condition.”

It’s akin to searching for a specific item in a vast expanse, as statistically, these specific variants are carried by very few individuals—sometimes just one.

Stefanie Heilmann-Heimback, the corresponding author of the study, explained their approach: “That’s why we employ gene-based analyses, which initially group together variants based on the genes where they are situated.”

Leveraging the UK Biobank and SKAT Methodology

To gather data, the researchers accessed information from the UK Biobank, focusing on a cohort of 72,469 men aged 39 to 82 years. They utilized the Sequencing Kernel Association Test (SKAT), a method for identifying rare genetic variants within a region related to observable traits (phenotype) in individuals.

Additionally, they used GenRisk, an open-source Python package that offers a framework for modeling the effects of rare functional genetic variants, particularly those occurring in less than 1% of the population.

They detected uncommon genetic variations in five genes: EDA2R, WNT10A, HEPH, CEPT1, and EIF3F. EDA2R and WNT10A had previously been considered potential genes based on examinations of common variants, but the findings validated their involvement as rare variants as well.

Stefanie Heilmann-Heimbach remarked, “Our study offers additional proof that these two genes play a role, and this is evident through both common and rare variants.”

Similarly, HEPH is located in a genetic region near EDA2R and the androgen receptor, which has historically shown the strongest association with hair loss in genetic studies.

HEPH, CEPT1, and EIF3F in the Spotlight

“However, HEPH has never been regarded as a potential gene,” stated Henne. “Our study suggests it might also have a role to play. CEPT1 and EIF3F genes are situated in genetic regions previously unrelated to male pattern hair loss. They are therefore entirely new candidate genes, and we propose that rare variants within these genes contribute to the genetic predisposition. HEPH, CEPT1, and EIF3F appear to be highly credible new candidate genes, given their documented roles in hair development and growth.”

Additionally, the findings indicate that genes known to cause rare inherited skin and hair disorders, like ectodermal dysplasia, might also be implicated in male pattern hair loss.

Further investigations are required to explore the interplay between rare and common genetic variants in male pattern hair loss and how rare variants contribute to its development. The researchers anticipate that the additional insights from their research will lead to improved, tailored treatment approaches for men affected by hereditary hair loss.

Read the original article on New Atlas.

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