Transgender People With Gender Dysphoria Could Have 'Rare' Gene Variants, Study Suggests

Scientists have shed new light on why people may have gender dysphoria—a condition experienced by some transgender people—by identifying "rare" gene variants linked with brain development.

By studying the DNA of 30 transgender men and women who had been diagnosed with gender dysphoria, they found what they described as 21 "rare" variants in 19 genes, in pathways in the brain associated with the sex hormone estrogen.

The pathways are thought to be important for shaping whether the brain is masucline or feminine. Before and after birth, the genes help to decide when estrogen is released, which contributes to masculinization of the brain, the researchers explained in their paper published in the journal Scientific Reports.

People who are assigned male at birth but later identify as female may not go through this process of masculinization, the team believes.
According to the authors, approximately 0.5 to 1.4 percent of people assigned male at birth and 0.2 to 0.3 percent of those assigned female at birth will develop gender dysphoria.

This is when a person feels distressed because the gender they were assigned at birth does not match their internal feelings. For example, a person with a penis who is assigned as a boy at birth, but who identifies as a girl. Some, but not all, transgender people experience gender dysphoria.

The study involved 13 transgender males and 17 transgender females who gave samples of their blood. They had all been diagnosed with gender dysphoria. From these samples, the team were able to examine the participants' DNA. They also used 88 cisgender individuals as the control group for their study.

As with any research, the study has limitations including that it involved only 30 individuals.

Co-author Dr. J. Graham Theisen, an obstetrician/gynecologist and National Institutes of Health Women's Reproductive Health research scholar at the Medical College of Georgia at Augusta University, told Newsweek this is larger than most other studies investigating this topic with the same methods.

The team is still enrolling patients for more studies, with the goal of recruiting at least 200 people. They pointed out transgender people can find it hard to access healthcare for gender dysphoria, because of a general lack of understanding regarding its potential biological basis. This study might help combat that, they said.

"Many transgender individuals recount knowing, as early as 5-years-old, that their internal sense of gender and their external sex did not match," Theisen explained.

"Because of this, we thought that there was almost certainly a biologic component to gender identity."

The authors stressed in the study that they were not looking for a so-called "transgender gene," which might wrongly suggest that those with this gender identity are ill in some way.

Theisen said gender is on a spectrum, in the same way that eye colour is. Rather, they wrote, the aim was to "understand the complexities of gender development through the lens of genetics."

A person's "gender identity is more likely the result of a complex interplay between multiple genes as well as environmental and societal factors," they said. The team acknowledged that categories like "transgender male" and "transgender female" alone aren't enough to describe individuals who don't identify as cisgender. For instance, others might identify as non-binary, or in numerous other ways.

"While, in some individuals, a single genetic variant may be sufficient to result in gender dysphoria, it does not follow that that particular variant would be necessary or sufficient to cause gender dysphoria in the population at large," they wrote.

Theisen said: "The primary goal of our research is to gain a better understanding of the biologic component contributing to the spectrum of gender identities, and thus help our patients to gain a better understanding of themselves. Beyond that, we believe that with this enhanced understanding, we will be able to counter the discriminatory narrative that gender identity is a choice."

Theisen invited transgender individuals to take part in an online survey collecting their opinions on genetic research in this area.

Simona Giordano, an expert in gender identity and Reader in Bioethics at The University of Manchester Law School, who did not work on the study, told Newsweek: "A number of studies conducted in the last few decades suggest that gender identity and gendered behaviour might be, at least to an extent, influenced by prenatal hormone exposure. It is likely that a number of genes are involved in sex differentiation and development during prenatal life."

Giordano said such studies may help transgender people with gender dysphoria seek treatment, bolstering arguments that being transgender is not a lifestyle choice and "therefore people are entitled to help and support and social acceptance."

"But we should not need medical diagnosis to seek acceptance and provide help," she argued. "We provide medical help to women in labour because they suffer and there are means to alleviate their suffering—there is no need to suggest that suffering is pathological or being pregnant is pathology.

"Accepting people's differences at the condition that some biological factor is found as a 'cause' of that difference is a distorted idea of acceptance," Giordano said.

On the other hand, Giordano argued that finding a biological basis risks leading some to argue that interventions should be developed to change these genetic variations, rather than people's bodies so they align with their gender identity.

"We are now speculating, but given that genome editing is now possible, one could argue that, once the gene variants responsible for gender dysphoria are found, one could 'repair' the faulty gene with a 'healthy' one, to prevent or cure gender dysphoria," she said.

"However, in this way, one would not really treat gender dysphoria but eliminate transgender people," said Giordano. "This way of resolving problems is like addressing racism by eliminating people of colour" which would be "outright wrong."

Giordano concluded: "There is value in research that tries to understand gender identification and sex differentiation. However, grouping people in discrete categories is problematic: the categories of trans and cisgender, male and female, lack precise contours.

"Research in this area, if performed, should be directed to enhance the understanding of gender identification in us all, not just in only some of us. Singling out transgender people as subjects of research risks, even if inadvertently, to increase stigma and social perception of gender minorities as deviant and thus social discrimination."