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Genetics of sexuality

Genetics of sexuality

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Where does sexual attraction come from?

Valentine’s Day is coming and that day has become synonymous with the celebration of romance, partnership, love… and potentially sex at the end of the romantic, seductive day. Of course, the reality often strikes far from the fantasy, but fulfilled sexuality is a normal expectation of a healthy lifestyle, and perhaps there is no other day throughout the year that we go to such lengths to please and seduce each other. So to celebrate this unique day, we want to start a tradition of writing on topics linked to the emotions and behaviours that we so eloquently try to portray to one another on this special day.

What better way to launch this tradition than to focus on the topic that fascinates us all: sex. And since this is a blog about DNA and genetics, what better way to start than to delve into the genetics of sexuality!

Sexuality is obviously complicated. Just recall how the first conversation on the topic went with your parents, or anyone for that matter. It is even more complicated when it comes to deciphering it genetically. Some components are obvious, such as how chromosomes will define the physiological sex appearance. But sexual orientation and behaviour are more complicated, and very little is actually known about genetic influence into how they are developed.

During the first trimester, the fetal expression of genes either on the X or Y chromosomes will result in the development of ovaries or testes. These will subsequently release hormones that will imprint the fetal developmental brain with sexual orientation commencing at the second trimester. But because of the time gap between genital development and brain imprinting, in theory biological events can occur that could produce differences in brain imprinting on a very wide spectrum for sexual orientation between masculine and feminine that is unrelated to the genitals produced from the genetic signalling in the early stages of fetal development.

Image of Merogenomics article quote on fetal development

In essence, the binary concepts that we define as heterosexuality or homosexuality would be at the extreme ends of this spectrum of possibilities, although the majority of humans appear to be near the area of heterosexuality. Along with the development of sexual orientation, there are also physiological changes, to the anatomy of the brain, bones, teeth, and even fingerprint patterns that can be correlated to one orientation or the other, independent of genital development. It also appears to correlate to childhood play patterns, body movement, speech patterns, and even the likelihood of eating disorders, self-objectification, and body dissatisfaction. You might associate these traits with one biological gender or the other, but they appear to be more closely linked to sexual preference than merely a gender.

Just to be clear, gender identity itself is independent of biological gender or sexual orientation. If you are curious about it, a comprehensive literature review about genetics influencing variation in gender identity, suggests that gender identity itself is a heritable multifactorial complex trait stemming from many regions of the genome. As is typical for complex traits, these DNA components can contribute to the development of the trait but do not determine the trait.

In essence, sexual orientation is not a learned behaviour and cannot be chosen, but rather is imprinted during fetal development and hence is an innate biological outcome that is immutable. One interesting example of this is observed in fraternal twins that are the opposite gender. The hormones of one child can diffuse into the amniotic fluid of the twin and potentially influence future sexual orientation. Depending on whose hormones will be influencing who, one of the twins of such pairs will have an increased likelihood of homosexual orientation. Likewise, outside sources of substances that affect the hormonal balance during gestation can influence future sexual orientation.

Image of Merogenomics article quote on twin pregnancy

Another fascinating example is a well-established observation that biological older brothers increase the odds of homosexual orientation. In other words, the more brothers you have, the more likely you are to be born gay if you are a male. It is believed to occur through the build-up of maternal antibodies to male-specific proteins which can influence the brain development in subsequent male pregnancies. In fact, one recent study from Canada appeared to identify the culprit as neuroligin 4 Y-linked protein (what a name!), a protein produced by a gene found on the Y chromosome, and expressed on the surface of the fetal brain cells. It is an adhesion molecule that has a role in cell-cell interactions in male brain development, and is now a primary candidate for maternal immune response affecting the sexual orientation of their sons.

What the genes are that are affected along this process of development of future sexual behaviour and how the DNA differences among people are regulated are both still unknown.

Image of Merogenomics article quote on homosexuality

One aspect of sexuality and genomics is how much we really want to do the deed itself. Like what are you really willing to do to get out there and get laid suggests that it may be in your genes too!


Watch out for that GWAS

One brand spanking (no pun intended), new study suggests that it might be. The research was a genome-wide association study, abbreviated in a less sexy manner to GWAS, that compared the sexual behaviour between more and less risk averse groups of people.

But first, what is GWAS?

Basically, GWAS studies compare two groups of people with differing characteristics, that we are curious about in order to see how they differ genetically. The characteristic can be anything we want really, provided that we can accurately measure it and separate people based on having this characteristic or not. Most often this is done for health-related issues, but it can truly be anything. So the accuracy of the identified genetic mutations (appropriately referred to as variants), that we then associate with that characteristic really depends on how accurately we have measured it in people, and divided people into the group that do not have it (our control group), versus those who do.

Image of Merogenomics article quote on genome-wide association studies

Because of this reason GWAS studies are not definitive in their findings, while the mutations that are found to be linked to a particular trait are only an association, and not a mutation that is causative of the trait. Further studies are required before an association can be considered causative. This, by the way, is one of the most common problems related to scientific findings and commercial DNA tests because, often times, DNA tests are done based on what is only an association between DNA mutation and a trait, but will be presented to the public as a definitive link.

Another problem is that the individuality of each of the DNA mutations that are associated to any particular trait usually have a very modest effect on that trait and therefore basically have almost no predictive value. It is very rare that DNA mutations through GWAS studies are uncovered that are actually measured to have a large overall effect on a trait. This is another serious issue of DNA tests that are commercially available that base their results on prior GWAS studies.

Image of Merogenomics article quote on complex traits

Nevertheless, GWAS studies have played their part in the process of the discovery of genetic mutations contributing to human traits, and are still being carried out typically on larger scales (in terms of the number of participants which increases their accuracy).


Kinky sex is in our genes?

That brings us to the fresh-off-the-press publication on a GWAS study related to risky behaviour, including sexual promiscuity, measured in the number of lifetime partners. In this way, 124 DNA mutations were uncovered that were related to general risk tolerance, and 117 DNA variants that correlated with increased sexual risk tolerance (based on 370K participants in the UK Biobank), albeit once again, all with tiny effects only. The genetic correlation between the uncovered overall data for risk tolerance and the self-reported risky behaviour was large, with the highest correlation observed for adventurousness (0.83 out of 1), followed by the number of sexual partners (0.52), and car speeding propensity (0.45). So if you are not getting laid as much as you would like, at least in a tiny fraction, you can blame your genes. And if you want to increase your chances, become a bad driver?

Interestingly enough, the risky behaviour mutations had no correlation with the age of one’s first sexual encounter, with a negative correlation observed, but did correlate with teenage conception (at 0.25). Another interesting and large correlation was with self-employment. Another trick to help you get laid more often? If it is not in your genes, at least you can pretend!

But seriously, it appears that can be done! When the uncovered mutations were analyzed for the biological effect of the affected genes, it pointed to the role of excitatory and inhibitory neurotransmitters in the brain. Therefore, how the brain is working is behind the risk tolerance observed in people. And how learning specific tasks can be used to alter brain neurotransmission, is an area of intense investigation, at least in animal models. It appears that through learning specific tasks, you can rewire your brain to work differently by altering how the DNA in your brain is used.

Image of Merogenomics article quote on brain training

This is also supported by another study implicating the role of epigenetics in sexual behaviour.

Epigenetics is the study of changes in how genes are used (and which can be heritable!), which are not governed due to changes in the DNA code itself, but rather how DNA can be enhanced through the attachment of secondary information on top of it. This is most often achieved through the attachment of chemicals on top of the DNA code, and these additional chemicals can subsequently influence how the DNA is actually used. The simplest chemical that is attached to DNA is a methyl group, and hence the modification of the DNA is referred to as “DNA methylation”. There are other epigenetic mechanisms of regulating DNA use besides DNA methylation, but we will leave those for now. While epigenetic changes can be heritable, they are typically affected by environment and lifestyle choices, thus pointing to a possibility that you can modulate how your DNA is used based on your own choices.

Image of Merogenomics article quote on epigenetics

In the first-ever such study, the association between DNA methylation and risky behaviours, including sexual promiscuity or unprotected sex in adolescents, was investigated. An association between one such site in the CALML3 gene was found, albeit a weak one. But as to how you supposed to execute this type of impact to benefit your own sex life will remain a mystery for now. If it helps, the same site methylation was also associated with a lack of exercise and substance use (cannabis, alcohol, smoking and illicit drug use), if you need a boost in the right direction, but perhaps don’t count on the quality of what you might score along the way. One has to wonder if some delinquent teenagers made up lies during the questionnaire about their sexual prowess to enhance their own image, and now we are getting all excited by some new epigenetic association.


Same-sex sex comes out of genetic closet

Another new GWAS study has also recently revealed four locations in the DNA associated with same-sex sexual experience. Once again, the UK Biobank data was used, comparing the genetics of more than 450K people who claimed to have exclusively heterosexual sexual relationships against nearly 27K people who reported at least one same-sex experience. The 23andMe data on nearly 70K participants was the other contribution (in case you ever wondered what happens with your 23andMe results). Two of these variants were specific to males, one of which was found in a region previously found to linked to male baldness. The other one is in the region linked to olfactory receptors. The sense of smell is believed to play a role in sexual attraction (in case you don’t feel like rewiring your brain, making sure you smell nice is a first good step). Two more variants were found in both genders.

A wild finding is that these variants also appeared to be associated with mood and mental health issues. That is not to say that sexual attraction to the same gender is attached to mental health issues – remember that in GWAS studies, we are looking at traits to see what are genetic associations that can be attributed to them. Perhaps these variants were commonly found in people with such issues because non-heterosexual behavior historically has been more likely to be discriminated against, and as a result could lead to depression in such individuals. This is a perfect example of how a mutation found in GWAS is only an association, and not necessarily prove to be causative. Correlation is not a causation. In this case, the mutations observed to be linked to mental health issues are not the cause of mental health issues, but potentially a completely different trait, with social influences contributing to the mental health problems. At this moment, which gene functions these mutations actually influence is still completely unknown.

Image of Merogenomics article quote on genetics influencing homosexuality

It gets even more complicated. These four variants are not found exclusively in people engaging in occasional or exclusive same-sex sexual activity. They are observed in heterosexuals as well, but when it is present, heterosexual people tend to have more sexual partners. The authors suggested that is one of the reasons why evolutionarily such variants might be around and provide a mating advantage. Again, these are only associations. But don’t be surprised if suddenly you will see an inappropriate DNA test hitting the market that will assess you for sexual preferences.


The G-spot mystery lingers

The above study was also another historical first: it was the first-ever genetic study conducted on the sexuality of homosexual women. But then that should not be surprising considering how little research into female sexuality has been done, compared to males. Heck, even the existence of the G-spot is still controversial in science, despite the fact that 84% of women believe in its existence and 66% of women report the presence of a G-spot in their vagina, although only 14% believe all women have it, and 70% think only some women have it. More recently, the analysis of nerve bundles and blood vasculature distribution support the existence of the G-spot (abbreviated from Gräfenberg spot, if you didn’t know), and finally for the first time an MRI was used to find the elusive G-spot. That appears like the equivalent of looking for a needle in a haystack!

But this is an article about genetics, so is there genetic support for the presence of the G-spot? You can imagine that is likely a highly understudied domain. In the one and only such study, one group of authors did attempt to study the heritability of a woman’s ability to find their G-spot (yes, you read that right), using 1,804 twins. No genetic component was uncovered, and the author’s concluded: “A possible explanation for the lack of heritability may be that women differ in their ability to detect their own (true) G-spots. However, we postulate that the reason for the lack of genetic variation-in contrast to other anatomical and physiological traits studied-is that there is no physiological or physical basis for the G-spot.” Disappointed? The 56% of women in this study who claimed to have found their G-spot probably would be.

Image of Merogenomics Figure on Average female sex

Adapted from Burri AV et al. 2010. J Sex Med 7(5):1842-52

Whether the G-spot is genetic or not, real or not, let’s see what these women had to say about their sex. Women who orgasm during intercourse 100% of the time were more likely to report a G-spot. Also if they experienced multiple orgasms, were more satisīŦed with their sexual experiences and their relationship with their partners, fantasized more about sex, or were comfortable with erotic material and talking about sex-related issues, they were more likely to report presence of a G-spot. You probably see the trend, and the authors concluded that a “perception of having a G-spot is a function of non-physiological factors” such as an active imagination, attentiveness to inner feelings, or preference for sexual variety, all of which enhance the sexual sensation for a woman which could be misconstrued as having a G-spot.

For now, if you were planning to test yourself genetically for sexual behaviour traits, it is safe to say, it is not time for it any time soon. If you are seeking utility from your DNA, your best bet now is a clinical DNA test that will test you for your health issues predispositions or drug use, among some of the best benefits. Merogenomics can connect you with our best quality choices on the market. Valentine’s gift anyone?


This article has been produced by Merogenomics Inc. and edited by Kerri Bryant. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.


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