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Genetics of Hair Loss

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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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Dr. Bernstein on CBS - Eye on NY

Dr. Bernstein was interviewed by Dana Tyler, host of the television program “Eye on New York” on CBS, for the show that aired on April 17th. The wide-ranging interview was the feature in a 9-minute segment on hair transplantation and hair loss.

Below is a partial transcript from the interview.

Hair Loss – Men vs. Women:

DT: How big a problem is it, men versus women? We heard the statistics but is it worse for one group or the other?

RB: It seems to be worse in women emotionally. Statistically it’s obviously more common in men, but the pattern is very different. When men lose their hair they lose it mostly in the front. And they can start in two different patterns. One is in the temples and in the crown or it can just go front to back. That’s called patterned hair loss and it’s pretty obvious. Women have a more diffuse pattern so it would be many years before you even notice it.

DT: What about the influence we hear, if it’s your mother’s father or your mother’s grandfather was bald then therefore, men, you will be. Is there any truth to that?

RB: Like many myths there is a little bit to it. There is a slight predominance coming from the mother’s side of the family. There is something called an androgen receptor gene, that has been found on the X chromosome, which accounts for the slight difference between inheritance from the mother’s side versus the father’s side. But most of the genetics is on the regular chromosomes, called the autosomal chromosomes, which is the same from both sides. So you can get it from either your mother or your father or your uncles or grandparents.

Early Hair Loss:

DT: Age-wise. Are there certain times – I mean, we talked about earlier in the 30s, but some young men it happens earlier.

RB: It seems that when people start to lose their hair early, it has a tendency to be much more severe. So the people who start to thin around 16, 17 usually become very bald. Time is usually on your side if you have hair into your 30s and 40s, [it’s] more likely you’ll have a full head of hair.

Hair Loss in Women:

DT: Speaking about women and the reasons behind women’s hair loss. A little different than for men.

RB: It’s genetic, as with men for the most part, but there are two different systems. Where in men it’s related to androgens directly, which causes the front-to-back pattern, in women they have another enzyme pathway which kind of evens it out and keeps their hairline longer. Also, because women have a tendency to thin all over, their genetic hair loss can be mimicked by other things, such as diseases that cause hair shedding or thinning — so anemia, thyroid disease, medications such as birth control pills — all those things can also contribute to hair loss, and it seems that those factors are much more common in women than in men.

DT: And then in trying to determine if a woman is going through that, because there are more factors is it hard to figure out why there is the hair loss?

RB: It’s a little bit more difficult [in women]. The main thing that you do is to look at the hair diameters. In genetic hair loss the hairs have different diameters. In [conditions] like anemia, or where there is shedding on medication, the hair comes out at its root. Where people think of hair loss as losing hair, most of hair loss is thinning because the hairs are actually thinner in diameter.

Preventing Hair Loss:

DT: Preventing baldness… is there anything that can be done?

RB: There are… But it’s not what you think. It’s not hats and combs.

DT: Fertilizing your head. (laughs)

RB: There are two medications, main medicines. One is Propecia, or the generic term is called finasteride, and what that does is it blocks DHT. And DHT is what causes these hair follicles to gradually miniaturize, or get smaller, and disappear. And the other is Rogaine, which actually stimulates hair follicles directly. Unfortunately, Propecia can’t be used in women because it can cause birth defects during child bearing years and it can also stimulate breast tissue, but it is very effective in men.

DT: So what does a woman do?

RB: Well, Rogaine will help a little bit. Lasers can help a little bit, perhaps not as much as the initial studies have suggested. And then, once you’ve lost your hair, surgical options are available.

Hair Transplantation:

DT: Hair transplants. I know that’s a complicated procedure. And Dr. Max [Gomez] was talking about the art of it, too, when you’re finding someone. Tell me a little bit more…

RB: The main thing in hair transplants is really to determine who is a good candidate. And the interesting thing is that because of the pattern of [hair loss] in men, men usually have a very permanent area on the back and sides of the scalp. So when you move that to the front and top, it will continue to grow. Because women’s hair loss is more diffuse, the back and sides are not always stable. So, when you’re trying to decide if a woman is a good candidate, you have to make sure that the hair, where you get it from, is going to last their lifetime. And only a small percentage of women are really good candidates for that transplant.

The Future of Hair Restoration – Medications & Cloning:

DT: What about the future? Are you optimistic about new options on the horizon?

RB: First of all, new medications are coming out. Latisse is a medication that can grow eyelashes. And we’ve just started studying it in eyebrow hair, and it seems to grow eyebrows as well. There are studies to see if you can grow hair on the scalp. And it certainly will, it’s just whether it’s practical and how well it works. It probably will be of some benefit.

DT: There always is progress, right?

RB: Right. And then [there are] hair transplants where we can take individual follicles rather than having to take a long thin strip, although that still seems to give you the best volume. And then we’re trying to multiply hair. In other words, the limitation of transplants is always that we don’t have [as much] hair as we’d like. So we’re working on cloning. We’re working on multiplying hair that can actually be plucked from the scalp. So that [the original hair] will regenerate, and you then can get the plucked hair to grow into new hair follicles.

For more interviews with Dr. Bernstein, and other media appearances, visit our Bernstein Medical “In The News” section.

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After trading anecdotes with fellow hair loss physicians about how finasteride can reduce body hair in some patients, Sharon A. Keene, M.D. took the next logical step and asked whether finasteride might have a negative effect on patients who have body hair transplant (BHT) procedures.

In a review of scientific literature on whether finasteride effects body hair growth, Dr. Keene finds that current research is inconclusive.

Finasteride, the drug in the hair loss medication Propecia, works by blocking the 5-alpha-reductase type 2 enzyme (5-AR Type 2) which is needed by the body to covert testosterone to DHT. DHT causes common baldness, by making hair follicles shrink and eventually die.

In looking at DHT’s effect on body hair growth, current research strongly suggests that it does play a key role. Males born with a deficiency of 5-AR Type 2, and thus no DHT, have reduced, or absent, body hair growth (and no loss of scalp hair).

It would seem logical then, that when finasteride is used to re-grow hair on the scalp, it would also inhibit the growth of hair on the body. However, the genetic variation among people is too great to determine exactly how much of an influence it plays.

With this uncertainty of DHT’s effects on body hair, it is impossible to say, without further study, if finasteride would have the same effect on body hairs which are transplanted to the scalp. In Dr. Keene’s conclusion, she suggests:

A patient on finasteride for at least a year who undergoes BHT is probably safe to continue it, as remaining body hairs are apparently not sensitive to the effects of this drug.

You can read the full discussion and review of current research in the January/February 2011 issue of Hair Transplant Forum International, the official newsletter of the International Society of Hair Restoration Surgery (ISHRS).

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Dr. Christiano Interviewed on Alopecia, Hair Loss by New York TimesDr. Angela Christiano, a colleague of Dr. Bernstein’s at Columbia University, has been studying the causes of alopecia areata and genetic hair loss for many years. She, in fact, suffers from the disease as well.

The New York Times has published a question and answer interview with Dr. Christiano which covers her own struggle with alopecia, her research into the causes of genetic hair loss, and where she sees the field going in the future. Here is one exchange that offers a window into how her research is breaking new ground in the field of hair loss genetics:

Q. When were you able to actually do the study?

A. In 2008. We published our findings this past July. Ours was the first study of alopecia to use a genome-wide approach. By checking the DNA of 1,000 alopecia patients against a control group of 1,000 without it, we identified 139 markers for the disease across the genome.

We also found a big surprise. For years, people thought that alopecia was probably the stepchild of autoimmune skin diseases like psoriasis and vitiligo. The astonishing news is that it shares virtually no genes with those. It’s actually linked to rheumatoid arthritis, diabetes 1 and celiac disease.

Continued discovery by Dr. Christiano and others in the field of hair loss genetics will lead to clues like these, which will shape the future of hair loss treatment. The hope for hair loss sufferers around the world is that a medical treatment can be developed which will effectively cure androgenetic alopecia, or common baldness. There is a lot of ground to be covered and there are many studies yet to be conducted, but progress is being made.

You can read more about Dr. Christiano’s research on our Hair Loss Genetics News page.

Read the article and listen to a two minute audio stream of the interview at the NYT.

Photo c/o Ruth Fremson/The New York Times

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Q: Why do some people have a full head of hair into their seventies or eighties and others start to go bald in their late teens or early twenties? — E.Z., Darien, CT

A: The difference is genetic with the inheritance coming from either side of the family.

Although a person will have the genes his/her whole life, a gene’s expression (also called phenotype) can be quite variable. The factors that cause this variability are still unknown.

Read more about the Genetics of Hair Loss

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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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Q: I was reading the hair cloning area on your site and came across this passage:

“Donor cells can be transferred from one person to another without being rejected. Since repeat hair implantations did not provoke the typical rejection responses, even though the donor was of the opposite sex and had a significantly different genetic profile, this indicates that the dermal sheath cells have a special immune status and that the lower hair follicle is one of the body’s ‘immune privileged’ sites.”

Does this mean that I could get a hair transplant from someone else’s head of hair one day? Any type of hair?

A: Yes, in theory we will be able to use someone else’s donor tissue to clone hair – but the technology to actually do this is still years away.

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Q: Can stress accelerate hair loss? I am 25 and there is balding on my dad’s side of the family. I never had any thinning or hair loss till this year. I guess you can say I’ve been under a lot of stress. When I did notice shortly after my 25th birthday I started stressing even more, which led to more hair loss. It is thinner up front and it is thin on top. I have heard of some hair docs mapping your head for miniaturization, do you do this too? — E.W., Miami, FL

A: Yes. The presence of miniaturization (decreased hair diameter) in the areas of thinning allows us to distinguish between hair loss due to heredity (i.e. androgenetic alopecia) — in which hair progressively decreases in diameter under the influence of DHT — and other causes. The degree of miniaturization can be assessed using a hand-held instrument called a densitometer.

The pattern of hair loss and the family history are also important in the diagnosis.

Stress more commonly produces telogen effluvium, a generalized shedding that is not associated with miniaturization and is often reversible without treatment.

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Q: Why do some people have a full head of hair into their seventies or eighties and others start to go bald in their late teens or early twenties?

A: The cause is genetic and this poly-genetic trait can be inherited from the mother’s side, the father’s side, or both.

There is an old wives’ tale that it is inherited only from the mother’s parents. Although the inheritance can come from either side, it is actually greater from the mother’s side – but only slightly.

Read about Hair Loss Genetics

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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.

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Robert M. Bernstein M.D. was asked to provide expert medical commentary in two hair transplant videos produced by Healthology. The topics included “Hair Transplantation Techniques” and “Using Cloning Techniques in Hair Transplantation”.

Healthology, the leading producer of broadcast and webcast programming that provides consumers with direct access to top medical experts, produced an important series of videos on hair loss. As Associate Clinical Professor of Dermatology, Columbia University College of Physicians and Surgeons, Dr. Bernstein was a vital part of the interview series.

Hair Transplantation Techniques

The first video that Dr. Bernstein was invited to take part in, focused on the various techniques used in surgical hair restoration. As a pioneer of Follicular Unit Transplantation, the filmmakers were eager to hear Dr. Bernstein’s thoughts on FUT:

“A major breakthrough in hair restoration came via identification that hair didn’t grow individually, but actually in small groups called follicular units. And these follicular units are naturally occurring groups of hair from one to four” Dr. Bernstein explained, “in modern hair transplantation, a procedure we call Follicular Unit Transplantation is used; we transplant the hair the way it actually grows in nature.”

This Healthology segment explored how the Follicular Unit Transplantation technique is also helping patients who want to improve the appearance of old transplants or scars.

“What we can do now is remove the old grafts, sew the holes closed where they’re transplanted, place those grafts under a microscope, divide them into individual follicular units and then place them back in the scalp the same day.” said Dr. Bernstein.

In addition to covering surgical hair restoration, the segment touched on the issue of medications for hair loss. Though some patients think getting a hair transplant means they can stop taking hair loss medications, Dr Bernstein illustrated why most physicians recommend using medicine along with surgery:

“Hair transplantation and medications do essentially different things. The main benefit of a transplant is to restore hair that’s been lost. The main benefit of medication is to prevent further hair loss.”

Using Cloning Techniques in Hair Transplantation

In this second Healthology video segment, on hair cloning, they invited Dr. Bernstein to take part in the discussion along with other distinguished guests; including Angela Christiano, PhD an Associate Professor of Dermatology and Genetics & Development at Columbia University.

This interesting segment explored how researchers are trying to find ways to make more follicles for hair transplant surgeons to work with. Research into cloning techniques shows it may be possible to create a virtually limitless supply of new follicles in the not too distant future. Dr. Bernstein provided some insights as to how hair restoration doctors might approach hair cloning in the future:

“The actual role of cloning in hair transplantation will depend upon how the cloning technology actually evolves. Initially, cloning may be used to supplement a regular hair transplant. We would use Follicular Unit Transplantation to give definition to a hairline and frame the face. Cloning would then be used to give the hair transplant bulk, by placing the cloned hair (which may not look as natural as normal hair) behind the transplanted hair.”

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