A receding hairline, a complete lack of hair from the crown, and ultimately, the classical horseshoe-shaped pattern of baldness: Previous research into male pattern hair loss, also termed androgenetic alopecia, has implicated multiple common genetic variants. Human geneticists from the University Hospital of Bonn (UKB) and by the Transdisciplinary Research Unit “Life & Health” of the University of Bonn have now performed a scientific investigation of the extent to which rare genetic variants may contribute to this disorder. For this purpose, they analyzed the genetic sequences of 72,469 male participants from the UK Biobank project. The analyses identified five significantly associated genes, and further corroborated genes implicated in previous research. The outcomes have now been published in the distinguished scientific journal Nature Communications.

Male-pattern hair loss is essentially the most common type of hair loss in men, and is essentially attributable to hereditary aspects. Current treatment options and risk prediction are suboptimal, thus necessitating research into the genetic underpinnings of the condition. So far, studies worldwide have focused totally on common genetic variants, and have implicated greater than 350 genetic loci, particularly the androgen receptor gene, which is situated on the maternally inherited X chromosome. In contrast, the contribution to this common condition of rare genetic variants has traditionally been assumed to be low. Nevertheless, systematic analyses of rare variants have been lacking. “Such analyses are tougher as they require large cohorts, and the genetic sequences have to be captured base by base, e.g., through genome or exome sequencing of affected individuals,” explained first creator Sabrina Henne, who’s a doctoral student on the Institute of Human Genetics on the UKB and the University of Bonn. The statistical challenge lies within the incontrovertible fact that these rare genetic variants could also be carried by only a few, and even single, individuals. “That’s the reason we apply gene-based analyses that first collapse variants on the idea of the genes by which they’re situated,” explained corresponding creator PD Dr. Stefanie Heilmann-Heimbach, who’s a research group leader on the Institute of Human Genetics on the UKB on the University of Bonn. Amongst other methods, the Bonn researchers used a sort of sequence kernel association test (SKAT), which is a well-liked method for detecting associations with rare variants, in addition to GenRisk, which is a technique developed on the Institute of Genomic Statistics and Bioinformatics (IGSB) on the UKB and the University of Bonn.

Possible relevance of rare variants in male-pattern hair loss

The research involved the evaluation of genetic sequences from 72,469 male UK Biobank participants. Inside this extensive data set, Bonn geneticists, along with researchers from the IGSB and the Center for Human Genetics on the University Hospital Marburg, examined rare gene variants that occur in lower than one percent of the population. Using modern bioinformatic and statistical methods, they found associations between male-pattern hair loss and rare genetic variants in the next five genes: EDA2R, WNT10A, HEPH, CEPT1, and EIF3F.

Prior to the analyses, EDA2R and WNT10A were already considered candidate genes, as based on previous analyses of common variants. “Our study provides further evidence that these two genes play a job, and that this happens through each common and rare variants,” explained Dr. Stefanie Heilmann-Heimbach. Similarly, HEPH is situated in a genetic region that has already been implicated by common variants, namely the EDA2R/Androgen receptor, which is a region that has consistently shown the strongest association with male-pattern hair loss in past association studies. “Nevertheless, HEPH itself has never been regarded as a candidate gene. Our study suggests that it may play a job,” explained Sabrina Henne. “The genes CEPT1 and EIF3F are situated in genetic regions which have not yet been related to male-pattern hair loss. They’re thus entirely latest candidate genes, and we hypothesize that rare variants inside these genes contribute to the genetic predisposition. HEPH, CEPT1, and EIF3F represent highly plausible latest candidate genes, given their previously described role in hair development and growth.” Moreover, the outcomes of the study suggest that genes which are known to cause rare inherited diseases affecting each skin and hair (equivalent to the ectodermal dysplasias) may play a job in the event of male-pattern hair loss. The researchers hope that the puzzle pieces they’ve discovered will improve understanding of the causes of hair loss, and thus facilitate reliable risk prediction and improved treatment strategies.

The research was supported by funding from the Medical Faculty of the University of Bonn. Prof. Dr. Markus Nöthen, 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” on the University of Bonn. The publication costs in open access format were funded by the DEAL project of the University of Bonn.