Research at the University Hospital of Bonn and the University of Bonn has increased our understanding of male pattern baldness by identifying the significant role of rare genetic variants. Analyzing data from more than 72,000 men, the study identified five main genes and paved the way for better treatment and risk assessment of this common condition.
Bonn researchers have identified rare genetic variants involved in male-pattern hair loss.
Previous research into male pattern baldness, or androgenetic alopecia, has identified several common genetic variants associated with the condition, including a receding hairline, loss of hair on the crown, and ultimately horseshoe pattern baldness.
Researchers at the University Hospital of Bonn (UKBB) and the University of Bonn’s Transplantation Research Unit “Life and Health” have recently conducted an extensive analysis to determine the role of rare genetic variants in contributing to this disorder.
For this purpose, they analyzed the genetic sequence of 72,469 male participants from the UK Biobank project. The analyzes identified five significantly associated genes and additional identified genes involved in previous research. The results have now been published in a famous scientific journal Natural relationships.
Challenges in studying rare genetic variants
Male-pattern baldness is the most common pattern of hair loss in men, and it is mostly caused by genetic factors. The current treatment options and risk prognosis are very good, so there is a need to research the genetic background of the condition.
To date, studies worldwide have focused primarily on common genetic variants, with more than 350 genetic loci, particularly the androgen receptor gene, located on the maternally inherited X chromosome. In contrast, the contribution of rare genetic variants to this common condition is traditionally thought to be low. However, systematic analyzes of rare variants are lacking.
UKB and University of Bonn researchers discover rare genetic variants involved in male pattern baldness: (left to right) PD Dr Stephanie Heilmann-Heimbach (Institute of Human Genetics), second author Rana Aldisi (Institute for Genomic Statistics and Bioinformatics), and Sabrina Heine (Institute of Human Genetics). Credit: University Hospital Bonn / Katrina Whiselsperger
“Such analyzes are more challenging because they require larger cohorts, and genetic sequences must be sequenced, for example, whole genomes or sequences of affected individuals,” said first author Sabrina Heine, a doctoral student at the institute. Human Genetics at UKB and University of Bonn. The statistical challenge is that these rare genetic variants can be carried by very few or even single individuals.
“That’s why we’re implementing gene-based analyzes based on the genes they’re found in, which fall first,” explained co-author Dr. Stephanie Heilman-Heimbeck, PhD, research team leader at the Institute of Human Genetics. at UKB at the University of Bonn.
Among other methods, the Bonn researchers used the Kernel Association Test (SKAT), a popular method for identifying associations with unusual variants, as well as GenRisk, a method developed by the Institute for Genomic Statistics and Bioinformatics. IGSB) at UKB and University of Bonn.
There may be rare variations in male-pattern hair loss.
The study involved analysis of genetic sequences from 72,469 male UK Biobank participants. In this extensive data set, geneticists from Bonn, together with human genetics researchers from the IGSB and the University Hospital Marburg, investigated rare gene variants that occur in less than one percent of the population.
Using modern bioinformatic and statistical methods, genetic variants between male-pattern hair loss and rare genetic variants were found in the following five genes: EDA2R, WNT10A, HEPH, CEPT1 and EIF3F.
Prior to the analyses, EDA2R and WNT10A were considered as candidate genes, based on previous analyzes of common variants.
“Our study provides further evidence that these two genes play a role and that this occurs in both common and rare variants,” explained Dr. Stephanie Heilmann-Heimbach. Similarly, HEPH is located in a genetic region with previously common variants in the EDA2R/Androgen receptor, a region that previous association studies have consistently shown a strong association with male-pattern hair loss. “However, HEPH itself has never been considered as a candidate gene. Our research suggests that it may play a role.” Sabrina Heine explained.
“The genes CEPT1 and EIF3F are located in genetic regions not yet associated with male-pattern hair loss. They are therefore entirely new candidate genes, and we hypothesize that rare variants in these genes contribute to genetic predisposition. HEPH, CEPT1, and EIF3F represent the most plausible new candidate genes given their previous roles in hair growth and development.
The study also suggests that genes known to cause rare genetic disorders that damage the skin and hair (such as ectodermal dysplasias) may also play a role in the development of male-pattern hair loss. The researchers hope that the pieces of the puzzle they have found will improve the understanding of the causes of hair loss, and thus facilitate reliable risk prediction and improved treatment methods.
Reference: “Analysis of 72,469 UK Biobank chromosomes links rare variants to male-pattern hair loss” by Sabrina Kathryn Heine, Rana Aldisi, Sugirthan Sivalingam, Lara Malin Hochfeld, Oleg Borisov, Peter Michael Kravitz, Carlo Madge, Marcus Maria Naughton, and Stephanie Heil. —Heimbach, September 22, 2023; Natural relationships.
DOI: 10.1038/s41467-023-41186-w
The study was supported by a grant from the Faculty of Medicine of the University of Bonn. Professor Dr. Marcus Naughton, director of the Institute of Human Genetics at UKB and co-author of the study, is a member of the Transdisciplinary Research Area (TRA) “Life and Health” at the University of Bonn. Publication costs in open access format were supported by the DEAL project at the University of Bonn.