Unlocking the Genetic Mysteries of Male Pattern Hair Loss: Rare Variants Revealed by University of Bonn Study"

Male pattern hair loss, also known as androgenetic alopecia, is a common condition affecting men, characterized by a receding hairline, crown hair loss, and the classic horseshoe-shaped balding pattern. While previous research has identified numerous common genetic variants associated with this condition, a recent study conducted by human geneticists from the University Hospital of Bonn and the Transdisciplinary Research Unit “Life & Health” of the University of Bonn has delved into the contribution of rare genetic variants. This comprehensive investigation, based on the genetic sequences of 72,469 male participants from the UK Biobank project, has shed light on five significantly associated genes, along with reinforcing the involvement of genes identified in earlier research. These findings have been published in the esteemed scientific journal Nature Communications.

Male-pattern hair loss is predominantly influenced by hereditary factors, making it crucial to explore the genetic foundations of the condition due to the limitations of current treatment options and risk prediction. Previous studies have mainly focused on common genetic variants, implicating over 350 genetic loci, notably the androgen receptor gene located on the X chromosome inherited from the mother. In contrast, rare genetic variants were thought to have a minimal role in this common condition. However, systematic examinations of these rare variants have been lacking, mainly because they necessitate large cohorts and the precise sequencing of genetic material, such as through genome or exome sequencing of affected individuals.

Sabrina Henne, the first author of the study and a doctoral student at the Institute of Human Genetics at the University Hospital of Bonn, explained that analyzing rare genetic variants is challenging as they may be carried by very few or even just one individual. To overcome this challenge, the researchers employed gene-based analyses that aggregate variants based on the genes they are located in. PD Dr. Stefanie Heilmann-Heimbach, the corresponding author and a research group leader at the Institute of Human Genetics at the University Hospital of Bonn, elaborated on the statistical methods used, including a sequence kernel association test (SKAT) and GenRisk, a method developed at the Institute of Genomic Statistics and Bioinformatics.

The study involved the examination of genetic sequences from 72,469 male participants in the UK Biobank. Within this extensive dataset, the researchers identified rare gene variants occurring in less than one percent of the population. Employing modern bioinformatic and statistical techniques, they discovered associations between male-pattern hair loss and rare genetic variants in five genes: EDA2R, WNT10A, HEPH, CEPT1, and EIF3F.

Prior to the study, EDA2R and WNT10A were already considered candidate genes based on previous analyses of common variants. Dr. Stefanie Heilmann-Heimbach noted that their study provides further evidence of the involvement of these two genes in male-pattern hair loss, driven by both common and rare variants. HEPH, situated in a genetic region previously implicated by common variants, was not considered a candidate gene before but is now believed to play a role. The genes CEPT1 and EIF3F, located in genetic regions not previously associated with male-pattern hair loss, are entirely new candidate genes. The researchers hypothesize that rare variants within these genes contribute to genetic predisposition, given their known roles in hair development and growth. Additionally, the study suggests that genes known to cause rare inherited diseases affecting both skin and hair, such as ectodermal dysplasias, may also play a role in male-pattern hair loss.

This research, supported by funding from the Medical Faculty of the University of Bonn, represents a significant step toward understanding the genetic causes of hair loss. It holds promise for improving risk prediction and developing more effective treatment strategies for male pattern hair loss, benefiting individuals affected by this common condition