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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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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

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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.

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Q: Is it worth getting the genetic test for balding?

A: You’re referring to Hair DX (hairdx.com), which costs about $150 and came to market in January of 2008 as the first test for androgenetic alopecia, aka male pattern baldness.

The test screens for variations in the androgen receptor gene on the X chromosome, the gene that is associated with male pattern hair loss. The purpose of the test is to identify persons at increased risk of developing hair loss before it is clinically apparent – so that medical intervention can be started early, when it is most effective.

It is important to realize that, at this point, there is just an association with this gene and hair loss; the cause and effect has not been proven and the association is not anywhere near 100%. A danger is that patients may overreact to the relatively incomplete information that the test provides. It is best to have the test performed under a doctor’s supervision, so that it can be put in the context of other information that the physician gleans through a careful history, physical and a densitometry hair evaluation. As of this posting, genetic testing for hair loss is not permitted in New York State.

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Most medical conditions can best be addressed with early diagnosis. Genetic hair loss is no different. A test now has the ability to identify whether or not you may be genetically predisposed to hereditary male pattern baldness (Androgenetic Alopecia).

The HairDX genetic test offers information that can aid you and your doctor in making an informed decision about the treatment of your hair loss.

This test is not a substitute for an examination by a physician experienced in the diagnosis and treatment of hair loss. It offers one more bit of information that, in the context of other data (such as hair loss pattern, scalp miniaturization and family history) can help guide you and your doctor to formulate an appropriate treatment plan.

How does this test work?

This new genetic test examines genetic variables (SNP) which are responsible for recognizing Androgen hormones in our bodies. These specific genetic variants of the X chromosome (the Androgen Receptor or AR gene) are found in 95-98% of bald men.

These genetic differences are associated with Male Pattern Baldness (MPB) and by identifying them; the onset of MPB might be better predicted. If a person is predisposed genetically to these chromosomal variations, they may be more likely to develop male pattern baldness prior to age forty.

The test consists of a simple swab of the inside of your mouth. The skin cells are then sent to the HairDX clinical laboratory for a confidential analysis.

How accurate is the test in predicting baldness?

HairDX tests for a genetic variant of a gene (the androgen receptor gene) found on the X-chromosome that is present in more than 95% of bald men. Sixty percent of patients with this variant experience male pattern baldness before the age of 40. Therefore, if a person has this gene, they would have an increased risk of significant pattern baldness.

Another, less common genetic variant of the same gene (present in about 1 in 6 men) indicates a greater then 85% likelihood that a person will not experience early onset pattern baldness. If a person is found to have this gene, they are unlikely to become very bald.

Why is the genetic test not 100%?

The androgen receptor gene identified thus far is only one of a number of genes that affect hair loss.

How does the test compare to information obtained from a history and physical exam by your physician?

An assessment of scalp miniaturization by an experienced physician using a densitometer, combined with a history and physical, appears to be a far more reliable way of predicting future hair loss. The genetic test can complement this information, but does not replace it.

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Q: What are the genes that cause male pattern baldness?

A: At this time the genes that actually cause hair loss are still unknown. However, there are two gene loci, recently identified, that appear to be associated with common baldness. The first is on the Androgen Receptor (AR) gene carried on the x-chromosome and the second is a non-sex chromosome 20p11.

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It has long been thought that the genes for common baldness come from the mother side of the family – explaining why a male whose maternal grandfather is bald is more likely to lose his hair than if his own father were bald. This observation was recently supported by the discovery of the androgen receptor (AR) gene which resides on the X-chromosome.

Remember, there are two sex chromosomes; X and Y. Females have two X chromosomes (XX), while males have one X and one Y chromosome (XY). This means that a male must get his X chromosome from the mother.

But we all have seen that some bald sons have bald fathers, even when no one on the mother’s side of the family has any hair loss. This suggests that the genetics of male pattern alopecia is more complicated, with multiple genes influencing hair growth. And it is likely that the inheritance of baldness is polygenetic, with relevant genes coming from both the x-chromosome of the mother and non-sex chromosomes of either parent. So where are the other genes?

Two independent research groups, one from England and the other Germany, both published in the journal Nature Genetics, have identified a gene locus p11 on chromosome 20 that seems to be correlated with male pattern hair loss, and since the gene is on a non-sex chromosome, it offers an explanation for why the inheritance of common baldness can be from either side of the family. It is important to emphasize that like the AR gene, the chromosome 20p11 locus has only been shown to correlate with hair loss. It is not been shown that either of these genes actually cause baldness.

Unlike many genes whose expression is one or the other (i.e. blue eyes or brown), the 20p11 variations tend to be additive; therefore, men with one affected copy will have a 3.7 fold increase in the chance of having early hair loss and those with two copies a 6.1 fold increase. Men with both the chromosome 20p11 variation and the AR gene will have a seven-fold increase of developing male pattern hair loss at an early age. This gene combination occurs in about 15% of Caucasian men.

The mainstay of predicting future hair loss is with a Densitometer – an instrument used by physicians to measure changes in hair shaft diameter (miniaturization). According to Dr. Robert Bernstein, “Looking at hair shafts under a microscope can spot shrinkage years before it is apparent – we can pick it up when kid are still teenagers.” Early diagnosis is important in androgenetic alopeica because medication is useful only if the hair loss is not too advanced. The genetic studies are significant in that they supply the physician with one more piece of information when developing a master plan for treating a person’s hair loss. See the article in the Wall Street Journal titled, Hair Apparent? New Science on the Genetics of Balding.

While researchers consider these latest discoveries to be of significant merit, caution must be made since these genes are felt to be associated with hair loss, but not yet shown to be causative. More importantly, the associations are not absolute. A clinical evaluation is still the most reliable indicator of future hair loss. Finally, the ability to identify associated genes does not suggest that a “cure” for male pattern baldness is imminent.

Reference
“On the Genetics of Balding,” Wall Street Journal, Vol. 4 – October 1, 2008.

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