Trans Genes?

By Monica Cheung
May 6, 2020
Silhouette of a woman and a man

After weeks of heated debate, on February 26, 2020, the Idaho state House passed a bill banning transgender female athletes from participating school sports on female teams on and  the bill will soon enter the Senate. Meanwhile, Arizona is trying to pass a similar bill and South Dakota’s Senate is debating a ban on treatments for transgender teens. While Rep. Barbara Ehardt of Idaho insists that the goal of such a bill is to ensure continued opportunities for female athletes, it cannot be denied that transgender culture has become a highly polticized and polarized issue. But does it have to be?

Scientists might have a different answer to that question. Researchers at the Medical College of Georgia at Augusta University now suggest that they have identified 21 gene variants that could link to gender dysphoria. Gender dysphoria– a condition where an individual’s assigned sex does not agree with their expressed gender, could lead to major distress and functional impairment without the necessary support. Members of the transgender community might experience gender dysphoria but the condition could improve or even resolve as they progress through their journey.

"Twenty-one variants in 19 genes have been found in estrogen signaling pathways of the brain critical to establishing whether the brain is masculine or feminine," says Dr. J. Graham Theisen, the lead author of the paper. The genes studied in this research are responsible for the masculinization of the brain right before and after birth. As a large portion of human brain development actually happens after birth, the gene expression during this period is exceptionally critical. 

The variants identified in this study suggest that gender dysphoria might have a deep biological root to it. This finding might mean that babies who are biologically male with these variants do not experience this important exposure to estrogen due to mutations. In other words, these babies’ brains do not experience the period of “brain masculinization”. Alternatively, babies who are born female might be exposed to a high level of estrogen during this period, leading to a more “masculine” brain. 

To understand the meaning of this study, it is important to first understand what “brain masculinization” actually means. Gender study in science could be difficult because we now live in a world where discrimination and misperception of gender cannot simply be excused. That being said, what is the biological basis for a “masculine brain”?

Animal studies could provide some additional insight to the problem. So let’s forget about the socially-imposed notion of what human males and females “should” do for a second. 

Sex-specific behaviors can be observed across many animal species in the nature, including our close relatives– primates. Typical male behaviors could range from mounting to increased aggression; and female behaviors could include special postures or even heightened sociality.

In this research at Augusta University, scientists studied cross-sex behaviors in mice. They found that disrupting these signaling pathways of estrogen in mice during the critical period of brain development could lead to increased chance of cross-sex behaviors. Male mice began to show a more female-like posture while mating and female mice performed mounting and thrusting behaviors. The result suggests that mutations at these specific genes could lead to significant behavioral change. 

In the case of humans, mutations at these specific genes could express themselves in a much more complex way. It is safe to say that not all members of the transgender community have the gene variants studied in this research. In fact, only around 0.5 to 1.4% of individuals born male and 0.2 to 0.3 % of individuals born female meet the criteria for gender dysphoria. But this study illustrates that there are a biological as well as cultural side to gender incongruence. 

"I think gender is as unique and as varied as every other trait that we have," Theisen says. Gene expression is not the only thing that affects the gender expression of an individual. But understanding the biological roots of gender dysphoria could have huge potential for legislations and treatment options in the future. Further scientific studies on gender identity could lay crucial groundwork for public perception of transgender people. 

Soon, there will be no excuse for people who choose to support or pass discriminatory bills like the ones in Arizona and Idaho. But the scientific community has to work closely with the LGBTQ community to ensure the appropriate presentation of such research work; and to fully evaluate the possible consequences that might follow. 

Gene variants provide insight into brain, body incongruence in transgender

Theisen, J.G., Sundaram, V., Filchak, M.S. et al. The Use of Whole Exome Sequencing in a Cohort of Transgender Individuals to Identify Rare Genetic Variants. Sci Rep 9, 20099 (2019).


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