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Transsexual gene link identified

Submitted by woman network on Wed, 29/10/2008 - 17:01. |

 

Australian researchers have identified a significant link between a gene involved in testosterone action and male-to-female transsexualism. DNA analysis from 112 male-to-female transsexual volunteers showed they were more likely to have a longer version of the androgen receptor gene.
 
The genetic difference may cause weaker testosterone signals, the team reported in Biological Psychiatry.
However, other genes are also likely to play a part, they stressed. Increasingly, biological factors are being implicated in gender identity. One study has shown that certain brain structures in male-to-female transsexual people are more "female like".
In the latest study, researchers looked for potential differences in three genes known to be involved in sex development - coding for the androgen receptor, the oestrogen receptor and an enzyme which converts testosterone to oestrogen.
 
Comparison of the DNA from the male to female transsexual participants with 258 controls showed a significant link with a long version of the androgen receptor gene and transsexualism.
 
Testosterone
 
It is known that longer versions of the androgen receptor gene are associated with less efficient testosterone signalling. This reduced action of the male sex hormone may have an effect on gender development in the womb, the researchers speculated.
"We think that these genetic differences might reduce testosterone action and under masculinise the brain during foetal development," said researcher Lauren Hare from Prince Henry's Institute of Medical Research.
 
Co-author Professor Vincent Harley added: "There is a social stigma that transsexualism is simply a lifestyle choice, however our findings support a biological basis of how gender identity develops."
 
Although this is the largest genetic study of transsexualism to date, the researchers now plan to see if the results can be replicated in a larger population. Terry Reed from the Gender Identity Research and Education Society said she was convinced of a biological basis to transsexualism.
"This study appears to reinforce earlier studies which have indicated that, in some trans people, there may be a genetic trigger to the development of an atypical gender identity.
"However, it may be just one of several routes and, although it seems extremely likely that a biological element will always be present in the aetiology of transsexualism, it's unlikely that developmental pathways will be the same in all individuals."

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Prince Henrys Press release

Submitted by kate on Wed, 29/10/2008 - 17:23.

Genetic link to gender identity

In the largest ever genetic study of male to female transsexuals Australian researchers have found a significant genetic link between gender identity and a gene involved in testosterone action.

From an early age people develop an inner sense of being male or female – their gender identity. Transsexuals however, identify with a physical sex opposite to their perceived biological sex.

DNA samples were collected from 112 male to female transsexuals and researchers compared genetic differences with non transsexuals. The results are published in the high impact journal Biological Psychiatry.

The researchers discovered that male to female transsexuals were more likely to have a longer version of a gene which is known to modify the action of the sex hormone testosterone.

“We think that these genetic differences might reduce testosterone action and under masculinise the brain during foetal development.” said researcher Lauren Hare.

For decades, there has been debate over the causes of transexuality. Early theories included psychosocial factors such as childhood trauma. More recent studies have indicated that family history and genetic aspects are linked to the development of gender identity.

“There is a social stigma that transsexualism is simply a lifestyle choice, however our findings support a biological basis of how gender identity develops.” said study leader Associate Professor Vincent Harley, Head of Molecular Genetics at Prince Henry’s Institute.

“As with all genetic association studies it will be important to replicate these findings in other populations” said Associate Professor Vincent Harley.

Researchers are now planning even larger genetic studies and are investigating a wider range of genes that may be related to gender identity.

Further Information

Androgen Receptor (AR) Repeat Length Polymorphism Associated with Male-to-female Transsexualism. Authors: Lauren Hare, Pascal Bernard, Francisco J. Sanchez, Paul N. Baird, Eric Vilain, Trudy Kennedy and Vincent R. Harley. The research will published in the Jan 2009 edition of Biological Psychiatry. Advance online publication date 27 Oct 2008.

This international study involved researchers at Prince Henry’s Institute, Monash Gender Dysphoria Unit, Monash University, Melbourne University, the University of California, Los Angeles in the USA. The research was funded by the National Health and Medical Research Council Australia and the US National Institutes of Health.

 

Prepublication Article Abstract

Androgen Receptor (AR) Repeat Length Polymorphism Associated with Male-to-Female Transsexualism

Lauren Hare, Pascal Bernard, Francisco J. Sánchez, Paul N. Baird, Eric Vilain, Trudy Kennedy, and Vincent R. Harley
Accepted: Aug 25, 2008

Abstract

Background: There is a likely genetic component to transsexualism, and genes involved in sex steroidogenesis are good candidates. We explored the specific hypothesis that male-to-female transsexualism is associated with gene variants responsible for undermasculinization and/or feminization. Specifically, we assessed the role of disease-associated repeat length polymorphisms in the androgen receptor (AR), estrogen receptor beta (ERβ), and aromatase (CYP19) genes.

Methods: Subject-control analysis included 112 male-to-female transsexuals and 258 non-transsexual male controls. Associations and interactions were investigated between CAG repeat length in the AR gene, CA repeat length in the ERβ gene and TTTA repeat length in the CYP19 gene and male-to-female transsexualism.

Results: A significant association was identified between transsexualism and the AR allele, with transsexuals having longer AR repeat lengths than non-transsexual male controls (p=0.04). No associations for transsexualism were evident in repeat lengths for CYP19 or ERβ ?genes. Individuals were then classified as short or long for each gene polymorphism based on control median polymorphism lengths in order to further elucidate possible combined effects. No interaction associations between the three genes and transsexualism were identified.

Conclusions: This study provides evidence that male gender identity may be partly mediated through the androgen receptor.

© 2008 Society of Biological Psychiatry

 

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