Male pattern hair loss may be linked to 5 gene variants

Evan Walker
Evan Walker TheMediTary.Com |
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Scientists have identified new genes that may lead to male pattern baldness. Bisual Studio/Stocksy
  • A study finds rare gene variants that may play a role in some male pattern baldness cases and confirms the involvement of two genes whose variants have been previously implicated.
  • Most male pattern baldness is genetic and may be treatable, especially if caught early.
  • Although the study focuses on rare variants, it nevertheless contributes to our knowledge of genes and male pattern baldness.

While male pattern baldness is typically associated with genetics, exactly which genes are involved continues to be an area of investigation. The condition’s medical name is androgenic alopecia. It affects around 80% of European men (and some women).

A new study identifies three previously unsuspected genes that may be involved in male pattern baldness while confirming the involvement of two other genes already presumed to be involved.

Male pattern baldness typically begins with a hairline that recedes before it eventually connects to a bald spot at the crown of the head. The hair between the temples and crown may then thin or no longer grow, leaving a band around the lower back and sides of the head. Not every male whose hairline recedes progresses to that final state.

While strictly cosmetic, the loss of one’s hair can factor into one’s sense of self. According to a 2005 survey of 729 men, hair loss was linked to feelings of depression and reduced self-confidence.

The International Society of Hair Restoration Surgery (ISHRS) estimated that 2,221,191 hair restoration treatments would occur in 2021. One report suggests that the global hair transplant market will be worth $53.17 billion by 2028.

A pair of early studies estimated that roughly 80% of male pattern baldness is due to genetic factors. Researchers later identified 600 genetic risk variants found at 350 genomic loci—positions within a genome.

Other researchers, using a data set from the UK Biobank, estimated in an association study that the identified variants accounted for about 39% of male pattern baldness and that the impact of rare variants was close to 0%. However, the design of the study meant the impact of rare variants was hard to quantify accurately.

In 2019, the UK Biobank released a large new data set that allowed the authors of the current study to perform an exome-based association study, using data from 72,469 men. (Exomes are the protein-coding portion of a genome.)

The new analysis confirmed a role for variants of the genes EDA2R and WNT10A and identified for the first time three additional genes: HEPH, CEPT1, and EIF3F.

All the studies described above detect associations between genetic variants and male pattern baldness and can not, therefore, directly establish causality.

The study is published in Nature Communications.

The study agreed with the previous estimate that these rare variants influence male pattern baldness in very few people.

“As for male pattern baldness, but also other common complex heritable phenotypic traits, it is known that common DNA variants do not explain all of the phenotyping variance. Therefore, people started to look into rare DNA variants, as this study did for MPB,” said Dr. Kayser.

Dr. Ken Williams, Jr., president of the American Board of Hair Restoration Surgery, who was also not involved in the study, suggests this tracks with his clinical experience.

“When I do my consultations with patients, I always look for these genetic patterns. I ask the patient oftentimes, ‘who has hair loss in your family?’ Sometimes it’s obvious: They’ll say, ‘Oh, my mom, my dad, my brother’. Sometimes they’ll say, ‘Oh, it’s my grandfather.’ But sometimes the patients will say, ‘Well, I don’t know that there is a history. Everyone has a lot of good hair,’” he said.

“So, you know, these patients could be [influenced by] these variants,” suggested Dr. Williams.

He added that patients whose hair loss does not appear to be genetic amount to about 5% of cases.

“Identifying these genes and the biological signaling pathways they are part of provides insights into the underlying biology, adding to the existing body of knowledge on [male pattern baldness]. This knowledge can be useful in improving prediction and therapy.”
— Sabrina Henne, first author

The first two genes identified in the study are WNT10A and EDA2R, which “are known regulators of the hair growth cycle, which is deregulated in male-pattern hair loss,” said Henne.

While the role of the remaining genes is unclear, Henne noted, “previous investigations into the functions of these genes suggest that they may influence hair growth through iron and phospholipid metabolism, respectively.”

EIF3F may have something to do with depigmentation. This occurs in male pattern baldness.

“As affected hair follicles miniaturize, causing the hairs to become finer and lighter,” Henne explained.

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