Fran was a teenager living in a small country town in New South Wales when she realised her gender identity was at odds with the one she was given at birth, based on her sex.

"When I discovered at the age of 15 that I had a transgender identity, I didn't feel safe to talk to anyone about it," she said.

"I had a fairly unsupportive family — there was a history of domestic violence."

Fran is now a mental health worker and peer support trainer. ( Supplied )

For a long time, Fran lived with depression, anxiety and gender dysphoria: a medical term used to describe the distress felt by people whose sense of being male or female differs from the gender they are assigned at birth (based on their sex).

"I ended up being very deeply closeted for around 20 years, and that led to mental health problems and breakdowns," she said.

In 2003, Fran moved to Melbourne to begin the process of transitioning.

"I had gender-reassignment surgery last year at the age of 46, and I'm continuing that process of being comfortable and learning to flourish in my sense of who I am," she said.

"The mental journey of self-acceptance has really been one of the dominating features of my life."

Evidence of potential biological basis

Fran is one of 380 transgender women who recently participated in an Australian-led study investigating the biological basis of gender dysphoria.

Researchers at the Hudson Institute of Medical Research in Melbourne analysed DNA of transgender women (male-to-female transgender people) and compared it to that of non-transgender men.

They found variations in four genes involved in processing sex hormones were significantly overrepresented in transgender women — suggesting a possible biological basis for gender dysphoria.

Lead author Vincent Harley said the study, published in the Journal of Clinical Endocrinology & Metabolism, was the largest and most comprehensive of its kind, identifying several new genes and genetic variations never before looked at in gender dysphoria.

"We propose these genetic variations could make some males less able to process androgen, causing the brain to develop differently — with areas that are less 'masculine' or more 'feminine' — which may contribute to gender dysphoria in transgender women," Professor Harley said.

"But this is speculation … We don't have evidence of under-masculinisation, or feminisation.

"We just know these [genetic] variants have, in other contexts, been associated with those features."

Jenny Graves, a geneticist at La Trobe University, who was not involved in the study, said although this area of research was relatively new, the study was well-controlled and robust.

"It is early days, but there is a strong feeling that there are going to be genetic factors involved," Professor Graves said.

"The reason for that is because people have done twin studies, and identical twins do have a higher incidence of being the same: 30 per cent of identical twins will be transgender if their other twin is a transgender.

"That means it's not entirely genetic, but there's a pretty strong basis of genetics in it."

She said the genetic variants identified in this study were likely to lower levels of male sex hormone androgen in the uterus before birth, albeit in slightly different ways.

"These genes will be active in adults too, but the most significant changes in the brain would probably be before birth."

Hopes to reduce discrimination

Professor Harley said the study added to a growing weight of evidence of a biological basis — genetic, neurobiological and endocrine — for transgender identity as part of human diversity.

"While it should not hinge on science to validate people's individuality and lived experience, these findings may help to reduce discrimination, lend evidence towards improving diagnosis or treatment, promote greater awareness and acceptance, and reduce the distress experienced by transgender people in our communities," he said.

"People with gender dysphoria have increased rates of depression, anxiety, eating disorders, self-harm and suicide."

A 2017 report found approximately three in four trans young people experienced anxiety or depression, four in five engaged in self-harm, and almost half had attempted suicide.

Fran said she hoped scientific research like this would help improve understanding and acceptance in the broader community.

"With the referendum last year on same-sex marriage, it really showed attitudes towards sexuality and gender diversity are changing, and changing in a really positive way," she said.

"My hope is that a better understanding of the genetics and mechanisms of transgender and gender-diverse experiences will lead to greater acceptance and celebration of difference."

Sally Goldner from Transgender Victoria said while the research was mostly positive, she had some concerns about how it might one day be used.

Sally Goldner, spokesperson for Transgender Victoria. ( Supplied )

"It's good to see [the research] back up what we already know — that we are who we are," Ms Goldner said.

"It's not so good if people don't seem to fit some sort of genetic test, if that was ever developed.

"I think the best thing we can still do is aim for inclusivity and respect for all people, rather than people feeling, 'Oh, now I'm justified'. No-one should ever have to justify themselves in that sense."

But Professor Harley said there was no intention to ever develop any kind of genetic test for being transgender, nor would one likely ever emerge.

"It's not what we're after here. What we're trying to understand is, 'Why do we feel the gender that we do?'" he said.

"'What's behind this amazing human diversity where gender identity is a spectrum?'"

Research in its infancy

Although the study provides a better picture of gender dysphoria and identity than previous research has, it's still a "very, very small picture", Professor Harley said.

"What makes you feel like a male or female is complex and involves interactions between many different genes, much like height, weight or blood pressure.

"However, while genes play a role, they are not the only factors involved in determining gender identity."

He said the next step was to do a bigger study with more people, examining more genes.

"I think by educating society and showing that there is a biological basis, that could help … empower people who are suffering this distress," he said.