Bernstein Medical Center for Hair Restoration

Dr. Bernstein Featured in Huffington Post on Hair Loss Genetics

Dr. Bernstein contributed to an article on hair loss genetics published in Huffington Post. In the article, “Sorry, You Can’t Just Blame Your Mother’s Father for Your Thinning Hair” Dr. Bernstein addresses the common myth that hair loss is inherited exclusively from the mother’s side of the family – and, more specifically, from your mother’s father. While your mother’s (or maternal grandfather’s) genes can be the culprit, the characteristics of your hair are influenced by many different genes that may come from either or both sides of your family.

The confusion stems from the fact that men inherit their X chromosome from their mother and a key gene involved in hair loss is found on the X chromosome.

Dr. Bernstein explains:

The androgen receptor gene is an X-linked gene, so there’s a slightly greater incidence of it following the mother’s side of the family than the father’s side, but genetic hair loss is polygenetic and the expressivity is very variable, so both sides can contribute to someone’s hair loss.

Dr. Christopher Cunniff, a clinical geneticist at Weill Cornell Medicine and New York-Presbyterian Hospital, added a comment that the genes most clearly identified as having influence on hair texture or color have not been found to be located on the X chromosome.

The article discusses hair loss genetics and a range of factors affecting the characteristics of one’s hair.

Image c/o: Ruigsantos via Getty Images

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Study More Accurately Predicts Severe Balding Risk Using New Genetic Profile

What are the chances that I will go bald? How bald will I be? Can I know for sure? These are among the most common questions we get from patients in our hair loss consultations. Despite extensive knowledge about the mechanisms and causes of androgenetic alopecia (common baldness), the answers to these questions have been a bit hazy. New research has sharpened the focus on the genetic mix that results in hair loss and has enabled more accurate predictions. A study published in February 2017 in the journal PLoS Genetics identified over 250 gene locations newly linked to hair loss. Using this information, researchers more accurately predicted severe balding compared to previous methods.

Background

We know that susceptibility to hair loss is driven by genetics. One in two men in their 50s experience some degree of balding, with that proportion increasing to over 60% of men aged 60 and over. We also know that one of the most important genes in hair loss, called the androgen receptor (AR) gene, is located on the X chromosome. Outside of that, knowledge of the precise genetic makeup resulting in baldness is sparse and there is wide variation in balding patterns. Some genetic tests, such as the HairDx test, have been developed to predict a patient’s risk of balding, but lack the ability to determine its severity. To date, the best method for predicting the extent of future hair loss is to have an experienced physician take a personal and family history and perform a physical examination that includes an assessment of miniaturization of scalp hair.

Developing a more thorough understanding of the complex genetic relationships that result in hair loss will be important in clinical practice as these relationships may help predict future hair loss and guide methods of treatment.

The Study

Researchers selected a pool of more than 52,000 men with male pattern baldness from UK Biobank. This is a massive database of over half a million people aged 40-69 years with information accumulated from 2006 to 2010. This pool was over four times the size of the previously largest hair loss study. Researchers applied a genome-wide association study (GWAS) to a cohort of about 40,000 men and identified 287 statistically important gene locations (loci) linked to varying degrees of baldness — more than 35 times the eight genetic signals found in the previous largest study.

Using this set of 247 loci on non-sex, or autosomal, chromosomes and 40 loci on the X chromosome, the researchers analyzed the remaining 12,000 men for predictive patterns. The results indicated that the predictive value of using this set of gene loci was 0.78 for severe hair loss, 0.68 for moderate hair loss, and 0.61 for slight hair loss. When the subject’s age was added, the predictive score improved to 0.79 for severe hair loss, 0.70 for moderate hair loss, and 0.61 for slight hair loss. Subjects whose individual scores, based on their genetic makeup, were below the mid-point of the range of scores were significantly more likely to have no hair loss than severe hair loss. By contrast, almost 60% of subjects whose individual scores were in the top 10% of the range of scores were moderate to severely bald.

While the predictions were not extraordinarily accurate – the authors characterized the accuracy as “still relatively crude” – they did show a distinct improvement in predictive accuracy over prior studies.

Summary

Hair loss is a serious concern for many people. Research shows that men with extensive hair loss may experience significant psychosocial impacts such as reduced self-image and reduced social interactions. Some studies have associated baldness with increased risk of prostate cancer and heart disease.

Understanding the complex factors that comprise the genetics of hair loss can help physicians potentially customize treatments based on a patient’s genetic profile and their risk of balding. Beyond that, diagnosing the potential severity of hair loss may help doctors get a head start on treating what could be related life-threatening conditions.

With large databases like UK Biobank, researchers can now drill down into this information and develop increasingly clear, highly granular data sets that can identify complex systems and potentially lead to improved treatments.

References

Hagenaars SP, Hill WD, Harris SE, Ritchie SJ, Davies G, Liewald DC, et al. (2017) Genetic prediction of male pattern baldness. PLoS Genet 13(2): e1006594. doi:10.1371/journal.pgen.1006594

Posted by Robert M. Bernstein M.D.

Is Genetic Hair Loss Linked to Other Diseases?

Q: There was a retrospective study by Lotufo et al. linking male pattern baldness to heart disease. Do you think there are other links like this for androgenetic alopecia? — J.L., San Francisco, CA

A: Family studies revealed both the androgen receptor locus on the X chromosome, as well as a new locus on chromosome 3q26. Association studies performed in two independent groups revealed a locus on chromosome 20 (not near any known genes) as well as the androgen receptor on the X chromosome.

So far, the genetic studies for androgenetic alopecia (AGA) have not revealed identification of a particular gene other than the androgen receptor, as well as the two candidate regions on chromosomes 3 and 20. Inasmuch as the androgen receptor can be involved in other diseases, this might be a feasible connection. Until candidate genes are identified that underlie AGA, it is impossible to predict where the commonalities might lie.

Excerpted from Angela Christiano, Hair Transplant Forum International 2011; 21(1): 14-15.

Read more about Hair Loss Genetics, and see some other Hair Restoration Answers posts on the topic.

Posted by Robert M. Bernstein M.D.

Genetic Markers in Male and Female Patterned Hair Loss

Rodney Sinclair, MBBS, FACD, MD.
University of Melbourne, Fitzroy, Australia.

SUMMARY of Dr. Sinclair’s Abstract from his presentation at the International Society of Hair Restoration Surgery, 2005 – Sidney, Australia

Twin studies have confirmed the strong heredity of androgenetic alopecia. The purpose of the present study is to explore the genetic basis of androgenetic alopecia by gene analysis. The study compared the sequence of several candidate genes between groups of individuals considered to be most and least genetically predisposed to androgenetic alopecia. Most likely are young males who already have a significant degree of baldness and least likely are those who are older and have no sign of hair loss.

The 5 alpha-reductase genes (SRD5A1 and SRD5A2), aromatase genes, Y chromosome and androgen receptor genes were analyzed. The authors found a significant difference in the frequency of a single base change in the coding region of the AR gene. These results provide good evidence for the involvement of AR in androgenetic alopecia.

Interestingly, 77% of non-bald men carry the version of the AR gene found in bald men. This suggests that the AR gene is necessary but not sufficient for causing baldness. This raises the possibility that other genes are acting in conjunction with AR. For instance, genes other than SRD5A1 and SRD5A2 that control levels of DHT production remain candidates. Given that 5 alpha-reductase is increased in balding scalp, these might include transcription factor genes which regulate the production levels of 5 alpha-reductase. Such transcription factor genes are yet to be identified. The many other genes, known and unknown, that are involved in androgen production, regulation and response may also be involved.

In addition to androgen-related genes, genes involved in patterning, signaling and hair follicle morphogenesis are other potential candidates for future research.

Posted by Robert M. Bernstein M.D.