Researchers in Bonn have identified a rare genetic mutation responsible for male pattern baldness.
Previous research on androgenetic alopecia, or androgenic alopecia, has identified several common symptoms associated with this condition, characterized by a receding hairline, hair loss on the top of the head, and ultimately a horseshoe-shaped hair loss pattern. Genetic variations have been identified.
Researchers from the University Hospital Bonn (UKB) and the University of Bonn’s interdisciplinary research unit Life & Health recently conducted a comprehensive analysis to uncover the role of rare genetic variants in contributing to the disease. carried out.
To this end, they analyzed the genetic sequences of 72,469 male participants in the UK Biobank project. The analysis identified five significantly associated genes, further corroborating the genes implicated in previous studies. The results have now been published in a prestigious scientific journal. nature communications.
Challenges in researching rare genetic mutations
Male pattern hair loss is the most common form of hair loss in men and is primarily caused by genetic factors. Research into the genetic basis of this condition is needed, as current treatment options and risk prediction are suboptimal.
To date, research around the world has focused primarily on common genetic mutations, with over 350 genetic loci implicated, particularly the maternally inherited androgen receptor gene located on the X chromosome. ing. In contrast, the contribution of rare genetic variants to this common condition has traditionally been thought to be low. However, systematic analysis of rare variants is lacking.
“Such analyzes are more difficult because they require large cohorts and require base-by-base capture of genetic sequences, such as through genome or exome sequencing of affected individuals,” said the first author. , explained Sabrina Henne, a PhD student at the UK Institute. Human Genetics at UKB and the University of Bonn. The statistical challenge lies in the fact that very few or even single individuals may carry these rare genetic variations.
“That’s why we apply gene-based analysis, where we first analyze variants based on the gene in which they are present,” said corresponding author PD, research group leader at the Institute of Human Genetics. Dr. Stephanie Heilman-Heimbach explained. at the UKB of the University of Bonn.
The Bonn researchers are using, among other methods, a type of sequence kernel association testing (SKAT), a common method for detecting associations with rare variants, as well as genomic statistical and bioinformatics studies. using GenRisk, a method developed at (IGSB) UKB and the University of Bonn.
Possible association of rare mutations in androgenetic alopecia
The study involved analysis of genetic sequences from 72,469 male UK Biobank participants. Within this extensive data set, geneticists from Bonn, together with researchers from the IGSB and the Center for Human Genetics at Marburg University Hospital, examined rare genetic mutations that occur in less than one percent of the population.
Using modern bioinformatics and statistical methods, they discovered an association between androgenetic alopecia and rare genetic variants in five genes: EDA2R, WNT10A, HEPH, CEPT1, and EIF3F.
Prior to the analysis, EDA2R and WNT10A were already considered candidate genes based on previous analysis of common variants.
“Our study provides further evidence that these two genes play a role and that this occurs through both common and rare mutations,” explained Dr. Stephanie Heilmann Heimbach. Similarly, HEPH is located in a genetic region already implicated by a common variant, the EDA2R/androgen receptor, and this region is most associated with androgenetic alopecia in past association studies. These are areas where strong associations have been consistently shown. “However, HEPH itself has never been considered as a candidate gene. Our study suggests that it may also play a role,” explained Sabrina Henne.
“The genes CEPT1 and EIF3F are located in genetic regions not yet associated with androgenetic alopecia. Therefore, these are entirely new candidate genes, and rare mutations within these genes may contribute to a genetic predisposition. We hypothesize that HEPH, CEPT1, and EIF3F are highly plausible new candidate genes given their previously mentioned roles in hair development and growth.”
Additionally, the findings suggest that genes known to cause rare genetic disorders that affect both skin and hair (such as ectodermal dysplasia) may also be involved in the development of androgenetic alopecia. suggests that it is possible. The researchers hope that the pieces of the puzzle they have discovered will improve their understanding of the causes of hair loss, facilitating reliable risk prediction and improved treatment strategies.
Reference: “British Biobank Analysis of 72,469 exomes links rare mutations to androgenetic alopecia” Sabrina Katrin Henne, Rana Ardisi, Sugirtan Sivalingam, Lara Maren Hochfeld, Oleg By Borisov, Peter Michael Kravitz, Carlo Magi, Markus Maria Neten, Stefanie Heilman – Heimbach, September 22, 2023, nature communications.
DOI: 10.1038/s41467-023-41186-w
This study was supported by funding from the Faculty of Medicine of the University of Bonn. Professor Markus Nethen, Director of the Institute of Human Genetics at UKB and co-author of the study, is a member of the Interdisciplinary Research Area (TRA) ‘Life and Health’ at the University of Bonn. Publication costs in open access format were funded by his DEAL project at the University of Bonn.