Born this way? Researchers explore the science of gender identity

NEW YORK (Reuters) - While President Donald Trump has thrust transgender people back into the conflict between conservative and liberal values in the United States, geneticists are quietly working on a major research effort to unlock the secrets of gender identity.

A consortium of five research institutions in Europe and the United States, including Vanderbilt University Medical Center, George Washington University and Boston Children's Hospital, is looking to the genome, a person's complete set of DNA, for clues about whether transgender people are born that way.

Two decades of brain research have provided hints of a biological origin to being transgender, but no irrefutable conclusions.

Now scientists in the consortium have embarked on what they call the largest-ever study of its kind, searching for a genetic component to explain why people assigned one gender at birth so persistently identify as the other, often from very early childhood.

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Researchers explore the science of gender identity
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Researchers explore the science of gender identity
Dr. Vahram Haroutunian holds a human brain in a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri TPX IMAGES OF THE DAY
Human brains stored in formaldehyde are pictured at a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Dr. Vahram Haroutunian holds a human brain in a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
A bucket with a human brain stored in formaldehyde is pictured at a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Dr. Vahram Haroutunian holds a human brain in a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Human brains stored in formaldehyde are pictured at a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Human brains stored in formaldehyde are pictured at a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Buckets which hold human brains stored in formaldehyde are pictured at a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Dr. Vahram Haroutunian holds a human brain in a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Dr. Vahram Haroutunian holds a human brain in a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
A sign is pictured on a freezer that contains human brains at a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
Dr. Vahram Haroutunian holds a frozen slice of a human brain in a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
A worker checks the serial number on a slice of human brain before using a saw to cut a piece from the sample at a brain bank in the Bronx borough of New York City, New York, U.S. June 28, 2017. Picture taken June 28, 2017. REUTERS/Carlo Allegri
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Researchers have extracted DNA from the blood samples of 10,000 people, 3,000 of them transgender and the rest non-transgender, or cisgender. The project is awaiting grant funding to begin the next phase: testing about 3 million markers, or variations, across the genome for all of the samples.

Knowing what variations transgender people have in common, and comparing those patterns to those of cisgender people in the study, may help investigators understand what role the genome plays in everyone's gender identity.

"If the trait is strongly genetic, then people who identify as trans will share more of their genome, not because they are related in nuclear families but because they are more anciently related," said Lea Davis, leader of the study and an assistant professor of medicine at the Vanderbilt Genetics Institute.

The search for the biological underpinnings is taking on new relevance as the battle for transgender rights plays out in the U.S. political arena.

One of the first acts of the new Trump administration was to revoke Obama-era guidelines directing public schools to allow transgender students to use bathrooms of their choice. Last week, the president announced on Twitter he intends to ban transgender people from serving in the military.

A Quinnipiac University poll released on Thursday found 68 percent of Americans say transgender people should be allowed to serve in the military, an even larger majority than the 58 percent found in a Reuters/Ipsos poll last week.

21 PHOTOS
The faces and stories of transgender people around the world
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The faces and stories of transgender people around the world
Penelope Patterson does a one-handed push up at his home in Brooklyn, New York, U.S. December 13, 2016. Jodie Patterson's 3-year-old, Penelope, was brooding and angry until one day she asked her child what was wrong. Penelope, who was assigned female at birth, was upset "because everyone thinks I'm a girl," but he said he was really a boy. "I said, 'However you feel inside is fine.'" Patterson recalled from their home in Brooklyn. "And then Penelope looked at me and said, 'No mama, I don't feel like a boy. I am a boy.'" Almost immediately, Patterson embraced the reality that Penelope was a transgender boy, and by age 5 he was going to school as a boy. Today, at age 9, Penelope is happy and healthy as a boy who loves karate and super heroes and decided to keep his birth name. REUTERS/Brendan McDermid
Actress Laverne Cox walks in a Donna Karan creation during a presentation of the Go Red for Women Red Dress collection during New York Fashion Week February 13, 2015. REUTERS/Lucas Jackson (UNITED STATES - Tags: FASHION SOCIETY ENTERTAINMENT TPX IMAGES OF THE DAY)
Charlie Lowthian-Rickert, 10, who is transgender, is kissed by her father Chris following a news conference announcing that Canada will introduce legislation to protect transgender people from discrimination and hate crimes, on Parliament Hill in Ottawa, Canada, May 17, 2016. REUTERS/Chris Wattie. TPX IMAGES OF THE DAY
Joe Wong, 31, poses for photograph at his apartment in Bangkok April 3, 2015. Joe Wong, a 31-year-old transgender man from Singapore, underwent surgery to remove his breasts in 2007 and legally changed his name from Joleen to Joe. He had his uterus removed in 2009, and is legally recognised as a male. Wong is one of the many lesbian, gay, bisexual and transgender people in Asia who faced abuse and violence from his family. To escape the violence and find acceptance, many LGBT people migrate abroad - including Wong, who moved to Bangkok, where he currently works for the rights group, the Asia Pacific Transgender Network. To match Thomson Reuters Foundation Feature GAY-RIGHTS/ASIA Picture Taken April 3, 2015. REUTERS/Athit Perawongmetha
Transvestite Tiffany, 19, shows a scar of a knife attack in Tegucigalpa March 10, 2011. According to leaders of LGBT organizations (lesbians, gays, bisexuals and transgenders), 34 people have been murdered in the last 18 months. The U.S. embassy and United Nations Programme on HIV/AIDS (UNAIDS) have requested the government to investigate the murders and safeguard the rights of the LGBT community, local media reported. REUTERS/Edgard Garrido (HONDURAS - Tags: SOCIETY CRIME LAW)
Geraldine Roman, a transgender congressional candidate, (C) is greeted by her supporters during a "Miting de Avance" (last political campaign rally) for the national election in Orani town, Bataan province, north of Manila in the Philippines May 6, 2016. REUTERS/Romeo Ranoco
Former Olympian Caitlyn Jenner arrives for the "Glamour Women of the Year Awards," where she was an award recipient, in the Manhattan borough of New York November 9, 2015. REUTERS/Carlo Allegri
Chahat, a member of the transgender community, prepares for Shakeela's party in Peshawar, Pakistan January 22, 2017. REUTERS/Caren Firouz SEARCH "PAKISTAN TRANSGENDER" FOR THIS STORY. SEARCH "WIDER IMAGE" FOR ALL STORIES.
Qian Jinfan, an 84-year-old transsexual who prefers to be addressed as "Yiling" holds up a photo taken at the age of 59, in the town of Foshan, in southern China's Guangdong province, July 6, 2012. Qian, who told Reuters during an interview that she always felt she was a woman and experimented with hormone cream, tablets and injections at the age of 60, is believed to be the oldest transsexual to live openly in China. The retired Chinese Communist Party official said she would not undergo a sex-change operation until it fully guaranteed her a female body that was complete with a woman's bodily functions. She admitted her days may be limited, but hopes that speaking to the media can help break down traditional assumptions and initiate discussions about transsexuals in society. About 2,000 people in China have undergone sex-change surgery and up to 400,000 could be considering one, according to a report in 2009 by state newspaper China Daily. Picture taken July 6, 2012. REUTERS/Tyrone Siu (CHINA - Tags: SOCIETY TPX IMAGES OF THE DAY)
Tanya Walker, a 53-year-old transgender woman, activist and advocate, gives an interview at her apartment in New York City, U.S. September 7, 2016. Picture taken September 7, 2016. REUTERS/Brendan McDermid TPX IMAGES OF THE DAY
Renee Richards poses for a portrait at her home in Carmel, New York March 25, 2015. More than three decades after putting down her tennis racquet, Renee Richards, 80, told Reuters she is still astonished she possessed the moxie to join the women's professional tennis tour after living the first 34 years of her life as a man. For all the frenzy around Olympian Bruce Jenner's reported decision to transition to a woman, the transgender pioneer Richards, born Richard Raskind, believes nothing could be tougher than what she endured in the 1970s. Picture taken March 25, 2015. To match Feature USA-TRANSGENDER/RICHARDS REUTERS/Mike Segar
Helena Vukovic, Serbian first transgender veteran army officer, poses for a picture in Belgrade, Serbia September 7, 2016. REUTERS/Marko Djurica
Nada Chaiyajit, a Thai transgender activist, 37, poses during an interview with the Thomson Reuters Foundation at a hotel in Bangkok, Thailand, November 28, 2016. Picture taken November 28, 2016. REUTERS/Athit Perawongmetha
Transvestite Julio Yoaris Alvarez adjusts his brassiere while getting dressed at his home as the world celebrates the International Day Against Homophobia in Havana May 16, 2009. From an early age, Alvarez dreamt of having a sex-change operation and is currently awaiting his turn for one under the Cuban health care system. The surgery, like all other health care in Cuba, will be free of charge for applicants. REUTERS/Claudia Daut (CUBA SOCIETY HEALTH)
Carly Lehwald sits with her son Ben at Carly's home in Chicago, Illinois, United States, May 30, 2015. Carly is Ben's father "Charlie", and transitioning to life as a woman is the basis for a new reality television show "Becoming Us". Picture taken May 30, 2015. REUTERS/Jim Young TPX IMAGES OF THE DAY TPX IMAGES OF THE DAY
Anna Grodzka, Poland's first transsexual lawmaker, attends an introductory session to the Polish parliament for newly elected lawmakers in Warsaw October 24, 2011. REUTERS/Kacper Pempel (POLAND - Tags: POLITICS)
Naz Seenauth, a transgender man, poses in New York October 22, 2014. Seenauth's driver's license says he is male. His birth certificate says he is female. The mismatch, he says, is deeply frustrating. New York City, where Seenauth was born and raised, does not accept that he is a transgender man and will not amend his birth certificate, for now at least, even though his doctor will attest to his gender. Picture taken October 22. To match Feature USA-NEW-YORK/TRANSGENDER REUTERS/Shannon Stapleton (UNITED STATES - Tags: HEALTH SOCIETY LAW)
Damian Jackson (C), 51, shows family members his new documents after changing his officially registered gender from female to male, in the City Hall in Amsterdam July 1, 2014. Jackson is among the first to obtain new documents on Tuesday, when a new law came into effect, legalising the registration of a transgender person's preferred gender in official state documents, including identity cards and passports. It eliminates the previous law, which required hormonal treatment, surgery or sterilization before any change in gender registration is allowed. REUTERS/Cris Toala Olivares (NETHERLANDS - Tags: SOCIETY LAW)
Audrey Mbugua, 31, Kenya?s most famous transgender campaigner, poses for a photograph in her garden in Kiambu, outside the capital Nairobi, March 31, 2015. Audrey Mbugua will not say whether it was a razor blade, pills or carbon monoxide that she used to try to kill herself. Born a male in Kenya and given the name Andrew, she felt trapped in the wrong body and started dressing in women's clothes while at university, attracting ridicule and rejection. After graduation, Mbugua was jobless, penniless and alone. Picture taken March 31, 2015. To match GAY-RIGHTS/KENYA REUTERS/Katy Migiro
Randy Dolphin and transgender activist Veronika Lee-Tillman, who will be Grand Marshal in San Francisco's gay pride parade, are married during a ceremony at City Hall in San Francisco, California June 28, 2013. The couple was married at City Hall with San Francisco Police Chief Greg Suhr giving away the bride. The U.S. Supreme Court on Wednesday handed a significant victory to gay rights advocates by ruling that married gay men and women are eligible for federal benefits and paving the way for same-sex marriage in California. REUTERS/Robert Galbraith (UNITED STATES - Tags: POLITICS SOCIETY)
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Texas lawmakers are debating a bathroom bill that would require people to use the bathroom of the sex listed on their birth certificate. North Carolina in March repealed a similar law after a national boycott cost the state hundreds of millions of dollars in lost business.

Currently, the only way to determine whether people are transgender is for them to self-identify as such. While civil rights activists contend that should be sufficient, scientists have taken their search to the lab.

That quest has made some transgender people nervous. If a "cause" is found it could posit a "cure," potentially opening the door to so-called reparative therapies similar to those that attempt to turn gay people straight, advocates say. Others raise concerns about the rights of those who may identify as trans but lack biological "proof."

"It's an idea that can be wielded against us, depending on the ideology of the user," said Kale Edmiston, a transgender person and postdoctoral scholar at the University of Pittsburgh specializing in neuroimaging.

Dana Bevan, a transgender woman, psychologist and author of three books on transgender topics, acknowledged the potential manipulation of research was a concern but said, "I don't believe that science can or should hold back from trying to understand what's going on."

Davis stressed that her study does not seek to produce a genetic test for being transgender, nor would it be able to. Instead, she said, she hopes the data will lead to better care for transgender people, who experience wide health disparities compared to the general population.

One-third of transgender people reported a negative healthcare experience in the previous year such as verbal harassment, refusal of treatment or the need to teach their doctors about transgender care, according to a landmark survey of nearly 28,000 people released last year by the National Center for Transgender Equality.

Some 40 percent have attempted suicide, almost nine times the rate for the general population.

"We can use this information to help train doctors and nurses to provide better care to trans patients and to also develop amicus briefs to support equal rights legislation," said Davis, who is also director of research for Vanderbilt's gender health clinic.

The Vanderbilt University Medical Center in Tennessee has one of the world's largest DNA databanks. It also has emerged as a leader in transgender healthcare with initiatives such as the Trans Buddy Program, which pairs every transgender patient with a volunteer to help guide them through their healthcare visits.

The study has applied for a grant from the National Institutes of Health and is exploring other financial sources to provide the $1 million needed to complete the genotyping, expected to take a year to 18 months. Analysis of the data would take about another six months and require more funding, Davis said.

The other consortium members are Vrije University in Amsterdam and the FIMABIS institute in Malaga, Spain.

PROBING THE BRAIN

Until now, the bulk of research into the origins of being transgender has looked at the brain.

Neurologists have spotted clues in the brain structure and activity of transgender people that distinguish them from cisgender subjects.

A seminal 1995 study was led by Dutch neurobiologist Dick Swaab, who was also among the first scientists to discover structural differences between male and female brains. Looking at postmortem brain tissue of transgender subjects, he found that male-to-female transsexuals had clusters of cells, or nuclei, that more closely resembled those of a typical female brain, and vice versa.

Swaab's body of work on postmortem samples was based on just 12 transgender brains that he spent 25 years collecting. But it gave rise to a whole new field of inquiry that today is being explored with advanced brain scan technology on living transgender volunteers.

Among the leaders in brain scan research is Ivanka Savic, a professor of neurology with Sweden's Karolinska Institute and visiting professor at the University of California, Los Angeles.

Her studies suggest that transgender men have a weakened connection between the two areas of the brain that process the perception of self and one's own body. Savic said those connections seem to improve after the person receives cross-hormone treatment.

Her work has been published more than 100 times on various topics in peer-reviewed journals, but she still cannot conclude whether people are born transgender.

"I think that, but I have to prove that," Savic said.

A number of other researchers, including both geneticists and neurologists, presume a biological component that is also influenced by upbringing.

But Paul McHugh, a university professor of psychiatry at the Johns Hopkins School of Medicine, has emerged as the leading voice challenging the "born-this-way" hypothesis.

He encourages psychiatric therapy for transgender people, especially children, so that they accept the gender assigned to them at birth.

McHugh has gained a following among social conservatives, while incensing LGBT advocates with comments such as calling transgender people "counterfeit."

Last year he co-authored a review of the scientific literature published in The New Atlantis journal, asserting there was scant evidence to suggest sexual orientation and gender identity were biologically determined.

The article drew a rebuke from nearly 600 academics and clinicians who called it misleading.

McHugh told Reuters he was "unmoved" by his critics and says he doubts additional research will reveal a biological cause.

"If it were obvious," he said, "they would have found it long ago."

(Reporting by Daniel Trotta; Editing by Marla Dickerson)

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