Most gene or gene variants previously explored have been associated with receptors for androgens, hormones more traditionally thought to play a role in male traits but, like estrogen in males, also are present in females. While genetics have been suggested as a factor in gender dysphoria, proposed candidate genes to date have not been verified, the investigators say. 'We want to understand what the genetic component of gender identity is.' 'We certainly think that for the majority of people who are experiencing gender dysphoria there is a biologic component,' says Theisen. Reproductive endocrinologist/geneticist Layman says his experience with taking care of transgender patients for about 20 years, made him think there was a biological basis. They also were rare or absent in large control DNA databases. The variants they found were not present in a group of 88 control exome studies in nontransgender individuals also done at Yale. The analysis was confirmed by Sanger sequencing, another method used for detecting gene variants. The extensive whole exome analysis, which sequences all the protein-coding regions of a gene (protein expression determines gene and cell function) was performed at the Yale Center for Genome Analysis. In fact, they already are exploring the pathways further and in a larger number of transgender individuals.įor this study, they looked at the DNA of 13 transgender males, individuals born female and transitioning to male, and 17 transgender females, born male and transitioning to female. 'We are saying that looking into these pathways is the approach we are going to be taking in the years ahead to explore the genetic contribution to gender dysphoria in humans.' 'This is the first study to lay out this framework of sex-specific development as a means to better understand gender identity,' Theisen says. He and Theisen are co-corresponding authors of the study in the journal Scientific Reports. While it's too early to definitively say the gene variants in these pathways result in the brain-body incongruence called gender dysphoria, it is 'interesting' that they are in pathways of hormone involvement in the brain and whether it gets exposed to estrogen or not, says Layman. They note that while this 'critical period' for masculinizing the brain may seem late, brain development actually continues well after birth and these key pathways and receptors already need to be established when estrogen arrives. These brain pathways are involved in regions of the brain where the number of neurons and how connected the neurons are typically differ between males and females. 'We have found variants in genes that are important in some of these different areas of the brain.' Layman, chief of the MCG Section of Reproductive Endocrinology, Infertility and Genetics in the Department of Obstetrics and Gynecology. 'It doesn't matter which sex organs you have, it's whether estrogen, or androgen, which is converted to estrogen in the brain, masculinizes the brain during this critical period,' says Dr. The goal of treatments like hormone therapy and surgery is to help their body more closely match where their brain already is.' 'Once someone has a male or female brain, they have it and you are not going to change it. 'They are experiencing dysphoria because the gender they feel on the inside does not match their external sex,' Theisen says. The negative emotional experience associated with this incongruence is called gender dysphoria. In natal females, it may mean that estrogen exposure happens when it normally wouldn't, leading to masculinization.īoth could result in an incongruence between a person's internal gender and their external sex. Variants investigators identified may mean that in natal males (people whose birth sex is male) this critical estrogen exposure doesn't happen or the pathway is altered so the brain does not get masculinized. Graham Theisen, obstetrician/gynecologist and National Institutes of Health Women's Reproductive Health Research Scholar at the Medical College of Georgia at Augusta University.īasically - and perhaps counterintuitively - these genes are primarily involved in estrogen's critical sprinkling of the brain right before or after birth, which is essential to masculinization of the brain. '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.

Transgender transformation sequences