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Rare gene variants linked to male hair loss identified

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Shillong, September 24: Researchers have made a significant breakthrough in understanding the genetic basis of male pattern hair loss, also known as androgenetic alopecia.

As per IANS, this common condition, characterized by hair loss in men, has been largely attributed to hereditary factors. However, existing treatments and risk prediction methods have limitations, prompting scientists to investigate the genetic components of the condition more comprehensively.

Previous studies have primarily focused on common genetic variants and have identified over 350 genetic loci associated with male pattern hair loss. Notably, the androgen receptor gene, located on the maternally inherited X chromosome, has been implicated in these studies.

In contrast, the role of rare genetic variants in this condition has traditionally been considered minimal. Systematic examinations of rare variants have been lacking due to the need for large cohorts and the precise sequencing of genetic sequences, such as through genome or exome sequencing of affected individuals.

Sabrina Henne, a doctoral student at the Institute of Human Genetics at the University Hospital of Bonn (UKB) and the University of Bonn in Germany, explained the challenges of analyzing rare variants, which may be carried by very few individuals, sometimes even just one.

To address this challenge, the Bonn researchers employed a sequence kernel association test (SKAT), a method for detecting associations with rare variants, along with GenRisk. Their study involved the analysis of genetic sequences from 72,469 male participants in the UK Biobank.

Within this extensive dataset, the geneticists identified associations between male pattern hair loss and rare genetic variants in five genes: EDA2R, WNT10A, HEPH, CEPT1, and EIF3F.

Among these genes, EDA2R and WNT10A had previously been considered candidate genes based on analyses of common variants. Dr. Stefanie Heilmann-Heimbach, a research group leader at the Institute of Human Genetics, noted that the study provides further evidence of the involvement of these genes through both common and rare variants.

HEPH is located in a genetic region previously linked to male pattern hair loss by common variants. The study suggests that HEPH itself may also play a role, despite not being considered a candidate gene before.

CEPT1 and EIF3F are located in genetic regions previously unassociated with male pattern hair loss, making them entirely new candidate genes. The researchers hypothesize that rare variants within these genes contribute to the genetic predisposition for the condition.

Moreover, the study indicates that genes known to cause rare inherited diseases affecting both skin and hair, such as ectodermal dysplasias, may also be involved in the development of male pattern hair loss.

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