Whether men become bald is usually determined by their genes: numerous genetic variants contribute to male pattern hair loss, some of which have already been discovered. Researchers have now identified new, rare gene variants that could also promote hair loss in men. These variants lie in five genes, only two of which were previously known to be potential causes of hair loss. The findings confirm that not only common but also rare gene variants can cause baldness. The study thus provides new insights into the causes of male hair loss.
The most common form of hair loss in men is androgenetic alopecia. In Europe, around 80 percent of men develop a receding hairline and bald spots on the back of their heads as they get older. This hair loss is usually hereditary and is due to changes in certain genes. Around 600 of these common gene variants are already known from previous studies. This includes, among other things, the androgen receptor gene on the X chromosome. However, the role that rare gene variants play in male hair loss has been little investigated. One reason for this is that in the case of rare variants, extensive sequencing of the genomes of affected men is necessary in order to obtain statistically significant results.
Hair loss variants in five genes
A team of human geneticists led by Sabrina Henne from the University of Bonn has now investigated this. For their study, the researchers analyzed around 72,500 genetic sequences from the UK Biobank, which came from British men between the ages of 39 and 82 with and without hair loss. They used modern bioinformatics and statistical methods to look for significant differences in the genes of both groups. For the analysis, the team used an established method and a self-developed method for detecting associations with rare gene variants. This enabled Henne and colleagues to compare rare gene variants that occur in less than one percent of the population.
The researchers identified five genes whose rare variants play an important role in hereditary hair loss in men: EDA2R, WNT10A, HEPH, CEPT1 and EIF3F. More common gene variants associated with hair loss were already known for the first two genes (EDA2R and WNT10A). “Our study increases the evidence that these two genes play a role, and that this occurs through both common and rare variants,” says senior author Stefanie Heilmann-Heimbach from the University Hospital of Bonn (UKB). The third gene (HEPH) is located in a region of DNA in which most of the already known gene variants for hair loss are located. “HEPH itself, however, was never discussed as a candidate gene – our study provides an indication that it could also play a role,” emphasizes Henne.
New candidate genes identified
The two genes CEPT1 and EIF3F, however, are located in genetic regions that were not previously associated with hereditary hair loss. “They are therefore completely new candidate genes, with the hypothesis that rare variants within these genes contribute to the genetic predisposition,” explains Henne. However, according to the study, it is very plausible that the three genes HEPH, CEPT1 and EIF3F are associated with hair loss and baldness, as they are involved in the development and growth of hair. The results also suggest that other genes could also play a role in the development of male pattern baldness (WNT10A, HOXC13, DSP, LPAR6, ALX4, EDAR, CDH3, HR, SPINK5 and TSPEAR). It is already known that they can cause rare hereditary diseases that affect both skin and hair.
Overall, the findings of the study help to better understand the causes of hair loss in men. The researchers hope that in the future the risk of hair loss can be predicted more reliably and treatment options can be designed more individually.
Source: Sabrina Henne (University of Bonn) et al., Nature Communications, doi: 10.1038/s41467-023-41186-w