A rare Genetic variant associated with male pattern Hair Loss has been discovered.

A thinning hairline, complete hair loss from the top of the head and eventually the classic horseshoe shape of hair loss: previous studies of androgenetic alopecia, also known as androgenetic alopecia, have pointed to several common genetic mutations. Geneticists from the University Hospital Bonn (UKB) and the interdisciplinary research unit “Life and Health” at the University of Bonn are now systematically investigating how rare genetic variants are involved in this disorder. To do this, the team analyzed the genetic sequences of 72,469 men who participated in the UK Biobank project. The analysis identified five significantly associated genes, confirming the assumptions of previous studies. The results of the study were published in the scientific journal Nature Communications.

Male pattern baldness is the most common baldness in men and is largely due to genetic factors. Research into the genetic background of this disease is necessary because current treatments and risk predictions are suboptimal. To date, global research has largely focused on common genetic variants involving more than 350 loci, in particular the androgen receptor gene located on the X chromosome, which is maternally inherited. The contribution of rare genetic variants to the development of this common disease has traditionally been considered low. However, there has been no systematic analysis of rare gene mutations. As lead author Sabrina Henne (doctoral student at the Institute of Human Genetics, UKB and University of Bonn) explains, “such analyses are more difficult because they require large cohorts and an understanding of the nucleotide-to-nucleotide sequence of genes, for example by sequencing the genome and exome of diseased individuals.” The statistical challenge is that very few people, and possibly one person, can have such a rare genetic variant. We therefore apply gene analysis, which first classifies variants based on the gene in which the variant is present,” explains the study’s first author Dr. Stefanie Heilmann-Heimbach, head of the research group at the Institute of Human Genetics at the UKB University of Bonn. Among other methods, the researchers from the University of Bonn used a variant of the Sequence Kernel Association Test (SKAT), a common method for detecting associations with rare variants, and GenRisk, a method developed at the Institute for Genomic Statistics and Bioinformatics (IGSB) at UKB and the University of Bonn.

Possible relevance of rare variants in male-pattern hair loss

In this study, the genetic sequences of 72,469 male participants in the UK Biobank were analyzed. In this large dataset, geneticists from Bonn, together with researchers from the IGSB and the Center for Human Genetics at the University Hospital of Marburg, studied rare genetic variants found in less than 1% of the population. Using state-of-the-art bioinformatics and statistical methods, they found an association between male pattern baldness and rare genetic variants in the following five genes: EDA2R, WNT10A, HEPH, CEPT1 and EIF3F. Prior to the present analysis, EDA2R and WNT10A were already considered candidate genes based on previous analyses of common variants. Our study provides further evidence that these two genes play a role, and this is through both common and rare variants,” explained Dr. Stefanie Heilmann-Heimbach. In addition, HEPH is located in a genetic region that is thought to be already involved through common variants, namely the EDA2R/androgen receptor. However, HEPH itself has never previously been considered as a candidate gene. However, HEPH itself has never previously been considered as a candidate gene. This study suggests that HEPH may also play a role,” explained Sabrina Henne. The CEPT1 and EIF3F genes are located in a genetic region that has not yet been linked to male pattern baldness. “We therefore hypothesized that these genes are completely new candidate genes and that rare variants in these genes contribute to genetic susceptibility; HEPH, CEPT1 and EIF3F are very plausible new candidate genes given their previously reported roles in hair development and growth. In addition, the findings suggest that genes known to be responsible for rare genetic diseases affecting both skin and hair (e.g., ectodermal dysplasia) may also be involved in the development of male pattern baldness. The researchers hope that the pieces of the puzzle found will improve our understanding of the causes of hair loss and contribute to reliable risk prediction and better treatment strategies. The study was funded by the Faculty of Medicine at the University of Bonn; Prof. Markus Norten, director of the UKB Institute of Human Genetics and co-author of the study, is a member of the Interdisciplinary Research Area (TRA) “Life and Health” at the University of Bonn. The cost of the open access publication was funded by the DEAL project of the University of Bonn.