The Genetics of Hair

Baldness: More Complex Than You Might Think

From bald eagles to Bruce Willis, bald spots are a common sight and part of the fabric of our society. It’s often assumed that baldness has a genetic component to it, and that’s absolutely true; it does. But it’s also commonly believed that baldness is inherited from your maternal grandfather. That part isn’t entirely true. As with many concepts in genetics, there’s a lot more to it than that!

Both men and women experience hair loss, but research has historically focused primarily on male subjects (and efforts to link the two have shown that female pattern hair loss is not predicted by the same genetic markers). Because of this, significantly less is known about female hair loss. We do know that approximately 30% of males experience some degree of hair loss (including simple hair thinning or a receding hairline) by the age of 30, 50% by the age of 50, and 80% by the age of 70 1.

Male pattern baldness (MPB) is a condition where hair loss occurs in multiple parts of the scalp, ultimately leading to a bald region surrounded by hair in a horseshoe-like pattern 3.The process of going bald is more complex than simply hair falling out, though. For starters, individuals with MPB are known to have smaller hair follicles on their scalp. Hair follicles are made of multiple cell types, each one dedicated to a particular process in building hair, which is actually a long chain of proteins (mostly keratin, which you can read about here) outside those cells. These follicles are where hair gains its unique features like curliness and color. Individuals with MPB not only have smaller follicles, but those follicles produce less hair, which contributes to the hair thinning process. Eventually, these follicles die, which produces a bald spot 1-4.

Why Do Some People Go Bald While Others Don’t?

Large scale genetic studies have shown that DNA plays a big part in determining whether MPB will develop 2-4. A common saying is that hair loss can be traced back to a person’s grandfather on their mother’s side. While this isn’t entirely true, there is some genetic evidence behind it. One of the well-known genes related to hair loss is the AR gene which codes for the androgen receptor protein. Among other functions, this protein helps hair follicle cells detect androgen hormones (like testosterone) that circulate through the body. Testosterone and other androgens can affect when, where, and how much a person’s hair grows 1. The AR gene is located on the X chromosome, which means that, for males, it was inherited from their mother. While this seems to lend credence to the notion that baldness is inherited from a person’s maternal grandfather, research indicates that the story is more complex than that. Recent studies report that MPB is a polygenic condition, meaning there are many genetic variants involved2. In fact, many of the genetic variants associated with MPB are not located on sex chromosomes. When considered together, these variants have been found to be more predictive of MPB development than variants that are located on sex chromosomes 2.

Although scientists have found DNA variants that seem to predict the likelihood of MPB development, it’s not entirely clear how these minor changes in the DNA lead to hair loss. Many of these variants are located in or near genes involved in the process of forming and maintaining hair follicle cells, indicating that these changes somehow affect the biology of hair follicles. Lots of proteins are involved in making and maintaining hair follicles, and we need to take all of them into account if we want to find the most complete answer 1.

DNA cannot be used to predict everything about a person’s future, but it can be used to make useful estimates of how likely it is that a person will have certain physical traits. MPB is a good example of this. Scientists can determine how many MPB associated DNA variants a person has, and use them to estimate their likelihood of experiencing hair loss. Individually, each gene may be associated with slightly higher odds of going bald; however, a person’s chances increase with each additional variant they inherit. Some people inherit a specific combination of variants that increases their likelihood of developing MPB by 58%2. This kind of analysis—where multiple genetic variants are taken into consideration—is common in genetics and helps strengthen the predictive ability of some types of genetic tests.

So, what’s the bald truth of baldness? MPB can be inherited from either side of a person’s family. If it turns out that your DNA increases your chance of having MPB, who knows? You might just be the next Samuel L. Jackson.

Why are there so many different facial hair types?

Have you seen any notable beards or mustaches lately? If not, don’t worry—there’s still plenty of time left in Movember to gaze upon the exotic displays of hair that this month has to offer. Facial hair is nothing new, but it’s during Movember—a one month event aimed at raising awareness of men’s health issues—that we get to see just how diverse it can be: some people don’t seem to be able to grow any at all, while others are sporting a dense forest of hair just a few days after shaving. So what gives? Why is there so much difference in hair growth among people?

When we think of hair, we typically think of what’s known as terminal hair—the pigmented, longer hair fibers that grow on our scalps and eyebrows. But there’s another kind of hair, so-called vellus hair, that blankets the human body. In fact, the only truly hairless parts of our skin are our palms, the soles of our feet, our lips, and portions of our sexual organs 5,6. We tend to see ourselves as hairless because vellus hair is small and non-pigmented, which makes it nearly impossible to see. But it is there, and it’s these barely visible hairs that will give rise to the many different flavors of facial hair types.

During embryonic development, hair follicles—the tiny, bulb-like structures of specialized cells that produce hair fibers—are formed into patterns across our bodies. These patterns set the stage for hair growth later in life1-3. When we’re born, hair follicles are densely packed next to one another, but as we grow, other cells force their way between them causing them to spread out 6,7. This is partly how our hair styles are defined: the patterns formed during embryonic development mixed with the spacing out of hair follicles during growth. So if your beard is thick, patchy, or sparse, it may be due to the movement or number of hair follicles formed during development. It may also have to do with the transformation of vellus hair into terminal hair.

Initially, many of our hair follicles produce vellus hair, which is why babies appear relatively hairless 5-7. However, later in life and especially during puberty, hormones flood the body and affect many physical changes, including the transformation of vellus hair follicles into terminal hair follicles. It’s not entirely clear why some cells are sensitive to these hormones while others aren’t, but typically it’s the hair follicles in the pubic region, on the limbs, and on a person’s upper lip or jaw that are responsive 7,8 So if a person is able to grow a beard or mustache, it means their facial hair follicles were able to make the change from vellus to terminal hair.

Understanding how facial hair develops—from embryonic patterning to hormone driven changes—helps us understand how a person’s DNA may affect their Movember fur. Few studies have looked at the genetics of facial hair development in humans, but the few studies that have been done give us some clues.

One such study found that facial hair thickness in a group of about 6,600 Latin Americans was associated with a genetic factor affecting the EDAR gene 9. This gene has previously been shown to affect the architecture of hair follicles during embryonic development3. It’s possible, then, that changes in the DNA affecting the EDAR gene may influence a person’s hair growth features. To that end, the researchers found that EDAR is involved in defining the pattern of facial hair follicles in mice—suggesting that it likely does the same in humans 9. These findings tell us that heritable changes in the EDAR gene may be one of the reasons there is so much diversity in facial hair growth among people.

EDAR is not the first (and it likely won’t be the last) gene associated with various hair traits 5,7. Researchers are still in the early stages of understanding how DNA can influence various facial hair features, but these early findings give scientists promising directions for future studies. As research continues, we can be sure that the handlebars, flavor savers, Tom Sellecks, and many other varieties of facial hair will continue to make Movember a memorable month.

DNA: Nature’s Curling Iron?

To identify as a mammal, a creature must have hair. Scientists aren’t sure how it evolved, but it’s been speculated that hair is a modified version of reptilian and fish-like scales that mammals developed to help them adapt to life on land. For humans, hair may have once served an important role in helping our ancestors adapt to new environments; for example, hair helps us regulate our internal body temperature by insulating body heat in cold climates, and regulating perspiration in hot ones. Whether a person has straight or curly hair can be partially attributed to their DNA, but the science behind curly hair isn’t exactly straightforward.

Some people try in vain to get their hair to curl, while others struggle to straighten it out—a battle that may lie in our genetics. Evidence indicates that some populations of people are more likely to have curly hair if they inherit specific changes in their DNA sequence 10. One of these changes occurs in the DNA sequence coding for the gene TCHH, which produces a protein known as trichohyalin. Depending on the version of this gene that you inherit (along with multiple other genes), you may be more likely to have curly hair rather than straight hair 11.

But to understand how these genes might affect hair structure, we need to talk about what hair actually is: a long shaft made of protein, mostly a rigid structural protein called keratin. Long fibers of keratin are strung together and pushed out of the skin in structures that we know as hair. Typically, hair is broken down into two main units—the shaft and the hair follicle3. Hair follicles are little packages of specialized cells that each contribute to building a hair shaft. Within the follicles, some cells produce large amounts of keratin and then die. When these cells die, the keratin within them remains in place like a molding of the cell. These keratin molds are densely packed together, but they need to be linked with one another to give the hair strength, similar to how bricks need to be sealed together with mortar 12,13.

Hair follicle cells use the protein trichohyalin as a temporary molecular mortar of sorts, linking fibers of keratin to each other (as well as other structural proteins). The keratin shaft is then pushed out of the skin when cells below it begin to replicate, thereby forcing the hair out of the skin. Just before it’s pushed out of the follicle, enzymes break down the trichohyalin which allows the hair to grow out 13.

Scientists are still working out what causes hair to be curly 10. Some evidence indicates that an asymmetrical hair follicle will result in uneven pressure from the replicating cells. This asymmetrical pressure may then cause the hair to curl and kink, giving it the curly look. Genetic research points to the trichohyalin protein as a contributing factor as well 10. It’s not clear how changes in the TCHH gene might affect the protein structure or function, much less how these changes lead to hair curl (or lack thereof), but it’s likely related to trichohyalin’s role in anchoring the hair fiber to the follicle. You can imagine how changes in the ability to evenly apply and remove this molecular mortar might affect the shape of the hair; however, we don’t yet know if these aspects are affected by the known changes in the TCHH gene.

Of course, your genes aren’t destiny, and there are plenty of tools that help us have whatever kind of hair we like. But the next time you reach for the curling iron or straightening brush, just remember: DNA might explain why you need it!

The Myth of the “Red Hair Gene”

Sometimes, genetics seems pretty straightforward. What color is your hair? Brown? Red? Blonde? You must have inherited the brown, red, or blond hair gene, right?

In reality, genetics is rarely simple—even when it comes to something as mundane as hair color. Genes can affect one another in many different ways. But understanding how a trait like hair color is determined can be helpful when reading through your DNA test results.

There are more than 20,000 different genes in your DNA which all work together to make you, you. Typically, people think of one gene giving rise to one trait. But we’ve come to find that very few of our traits work like this. Take hair color for example: there is no single brown, red, or blonde hair gene—it’s actually a whole network of genes that interact with one another to control the production of colorful pigments.

Someone who has black or brown hair is making large amounts of a dark pigment called eumelanin. The production and distribution of this pigment across a hair strand requires multiple steps, each of which involves different genes. To make eumelanin, the amino acid tyrosine has to go through multiple transformations, one of which involves the MC1R gene. This gene produces a protein of the same name which helps direct the chemical reactions. When the MC1R protein is made and active, it pushes the chemical reaction to produce the brown pigment eumelanin. But when it’s not being made or not working properly due to a change in the DNA, a red pigment known as pheomelanin is made. Variants have been found in the MC1R gene which cause less of its protein to be produced and results in build up of pheomelanin instead of eumelanin—and thus red-colored hair.

This is an example of a concept known as epistasis, which literally means “to stop or stand upon.” This term describes a common concept in genetics, which is that some variants can mask the effect of others. It helps to think of this like your commute to work. Let’s say you drive to work and you normally arrive at 8:00 am. To do this, your car has to be able to drive, and there has to be a smooth flow of traffic. Now let’s say there’s an accident on the highway which causes you to be 30 minutes late due to the resulting traffic jam. In this situation, the presence of the accident has changed the time you arrive. Based on this, you would predict that anytime an accident is present, you’ll arrive at 8:30. But, what if your car doesn’t start tomorrow? If that happens, it doesn’t matter whether there’s an accident on the highway—you won’t arrive at 8:00 or 8:30. In other words your car trouble has had an epistatic effect on the highway accident.

Returning to hair color, a variant in the MC1R gene that causes it to totally stop working will have an epistatic effect on most other variants—meaning if the MC1R gene stops working, it doesn’t matter if your body is trying to produce the brown pigment because without MC1R, it will produce a red pigment instead.

The concept of epistasis is important for more than just hair color: Researchers have found that epistatic interactions can affect many traits. For example, some variants have been identified to have an epistatic relationship that can have implications on lung cancer development 14.

So how does this help you understand your DNA test results? Oftentimes, you’ll see qualifying language in your results that says you are “likely” to have a certain trait. This is because concepts like epistasis, penetrance, and expressivity can all affect whether or not someone has a trait. It’s similar to driving to work where there are many ways for you to get delayed, but generally speaking, the presence of an accident will usually cause you to arrive at a different time. Based on experience, you can determine with a relatively high degree of accuracy what time you’ll get to work each day based on this. In that same way, it’s also possible to use your DNA to determine how likely it is that you will have a specific trait.

DNA, Hair, & Genetics

Scientists have made significant progress in understanding the genetics of hair, including texture, color, and likelihood of thinning. Variations in DNA may explain why some people have thicker eyebrows or are more prone to hair growth in certain areas.

While physical traits are often inherited, it’s important to note that genetics can be complex. Traits can be inherited from one parent or both, or environmental factors can influence the expression of certain genes.

Research on genetics and physical traits is ongoing and ever-evolving. Continued research and discoveries in this field may have implications for various areas, such as personalized medicine, forensics, and evolutionary biology.

Citations

1. Francesca, Lolli et al. “Androgenic alopecia: a review.” Endocrine 57:9-17 (2017): 10.1007/s12020-017-1280-y. Springer. Web. 11 Dec. 2017.
2. Hagenaars, Saskia P. et al. “Genetic Prediction of Male Pattern Baldness.” Ed. Markus M. Noethen. PLoS Genetics 13.2 (2017): e1006594. PMC. Web. 11 Dec. 2017.
3. Heilmann-Heimbach, Stefanie et al. “Meta-Analysis Identifies Novel Risk Loci and Yields Systematic Insights into the Biology of Male-Pattern Baldness.” Nature Communications 8 (2017): 14694. PMC. Web. 11 Dec. 2017.
4. Pirastu, Nicola et al. “GWAS for Male-Pattern Baldness Identifies 71 Susceptibility Loci Explaining 38% of the Risk.” Nature Communications 8 (2017): 1584. PMC. Web. 11 Dec. 2017.
5. Trueb, Ralph M. Hair Growth and Disorders. Springer-Verlag Berlin And Hei, 2008.
6. Held, Lewis I. “The Evo-Devo Puzzle of Human Hair Patterning.” Evolutionary Biology, vol. 37, no. 2-3, Apr. 2010, pp. 113–122., doi:10.1007/s11692-010-9085-4.
7. Mou, Chunyan et al. “Generation of the primary hair follicle pattern” Proceedings of the National Academy of Sciences of the United States of America vol. 103,24 (2006): 9075-80.
8. Randall, Valerie Anne. “Hormonal Regulation of Hair Follicles Exhibits a Biological Paradox.” Seminars in Cell & Developmental Biology, vol. 18, no. 2, 2007, pp. 274–285., doi:10.1016/j.semcdb.2007.02.004.
9. Adhikari, Kaustubh, et al. “A Genome-Wide Association Scan in Admixed Latin Americans Identifies Loci Influencing Facial and Scalp Hair Features.” Nature Communications, vol. 7, Jan. 2016, p. 10815., doi:10.1038/ncomms10815.
10. Westgate, Gillian E., et al. “The biology and genetics of curly hair.” Experimental Dermatology, vol. 26, no. 6, 2017, pp. 483–490., doi:10.1111/exd.13347. Web. 29 Nov. 2017.
11. Medland, Sarah E. et al. “Common Variants in the Trichohyalin Gene Are Associated with Straight Hair in Europeans.” American Journal of Human Genetics 85.5 (2009): 750–755. PMC. Web. 29 Nov. 2017.
12. Maderson, P. F. A. “Mammalian skin evolution: a reevaluation.” Experimental Dermatology, vol. 12, no. 3, 2003, pp. 233–236., doi:10.1034/j.1600-0625.2003.00069. Web. 29 Nov. 2017.
13. Alibardi, Lorenzo. “Perspectives on Hair Evolution Based on Some Comparative Studies on Vertebrate Cornification.” Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, vol. 318, no. 5, 2012, pp. 325–343., doi:10.1002/jez.b.22447. Web. 29 Nov. 2017.
14. MARCUS, MICHAEL W. et al. “Incorporating Epistasis Interaction of Genetic Susceptibility Single Nucleotide Polymorphisms in a Lung Cancer Risk Prediction Model.” International Journal of Oncology 49.1 (2016): 361–370. PMC. Web. 18 May 2018.