A recent study has uncovered more about the causes of hair loss in men by discovering a link between the condition and rare genetic variants in five genes.
Existing research had already identified numerous common genetic variants that can contribute to male-pattern hair loss, also known as androgenetic alopecia. The new study aimed to further our understanding of hair loss in men and rare genetic variants that could be contributory factors.
The most common form of male hair loss is male-pattern hair loss, which is widely believed to be caused by hereditary factors. Further research into the genetic causes of the condition is vital as current treatments and risk prediction are not sufficient.
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Human geneticists from the University Hospital of Bonn (UKB) and the Transdisciplinary Research Unit “Life & Health” of the University of Bonn examined genetic sequences from male participants to pinpoint five new associated genes and verify genes identified in previous research.
Past studies have mainly concentrated on common genetic variants and pinpointed more than 350 genetic loci linked to hair loss in men. Although rare genetic variants are not thought to contribute much to the condition, there has been a lack of research into these variants.
Sabrina Henne, first author of the study and doctoral student at the Institute of Human Genetics at the UKB and the University of Bonn, said: “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.”
Corresponding author PD Dr Stefanie Heilmann-Heimbach, a research group leader at the Institute of Human Genetics at the UKB at the University of Bonn added: “That is why we apply gene-based analyses that first collapse variants on the basis of the genes in which they are located.”
The researchers analysed the genetic sequences of 72,469 male UK Biobank participants for rare gene variants that occur in less than one per cent of the population. They discovered links between male-pattern hair loss and rare genetic variants in five genes (EDA2R, WNT10A, HEPH, CEPT1, and EIF3F).
Previous research had already established EDA2R and WNT10A as candidate genes. Dr Stefanie Heilmann-Heimbach explained: “Our study provides further evidence that these two genes play a role, and that this occurs through both common and rare variants.”
HEPH is part of a genetic region that was previously connected to common variants, namely the EDA2R/Androgen receptor, which has repeatedly been identified as having the strongest association with male-pattern hair loss.
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Sabrina Henne said: “HEPH itself has never been considered as a candidate gene. 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 hypothesise 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 study suggests that genes known to cause rare inherited diseases and affect skin and hair could also contribute to hair loss in men.
The study concluded: “Together, our findings broaden the male-pattern hair loss associated allelic spectrum and provide insights into male-pattern hair loss pathobiology and a shared basis with monogenic hair loss disorders.”
Researchers hope their findings will further understanding of what causes hair loss and contribute to improved risk prediction and treatments.
The study was published in Nature Communications.