In the first study of its kind, male sexual orientation can be predicted with nearly 70 percent accuracy with information from five segments of the human genome, according to research released Thursday.

If confirmed, the study will give more weight to suggestive but so far less than conclusive evidence that differences in DNA help determine whether people develop as heterosexual or homosexual. Other studies have found potential linkages, but have had trouble being replicated.

This study is the first to examine the effect of “epigenetic” changes in DNA, using pairs of identical twins, said UC Los Angeles researcher Tuck C. Ngun, the study’s first author. These are produced by alterations to DNA that turn genes on or off, but don’t alter the actual DNA sequence. The study was presented at the annual meeting of the American Society of Human Genetics in Baltimore.

Tuck Ngun ( / Tuck Ngun)


Environmental factors are believed to be involved in this long-running scientific debate, because the search for a so-called “gay gene” has failed to produce any single absolute genetic determinant. However, the technology necessary to perform detailed genomic comparisons among many people has only recently been developed.

Experts cautioned that the study surveyed a small number of people, and even if confirmed by further research, it doesn’t necessarily establish a cause.

Various observational or behavioral approaches have been developed to gauge sexual orientation, including who people choose as Facebook friends, facial shape, and “gaydar,” that nebulous ability to determine orientation based on a brief observation.

However, those studies don’t examine the biology underlying sexual orientation. The new research confines itself to the information present in the genome of those studied, comparing it to the declared orientation of study participants. Ngun said it evolved out of years of often-puzzling observations about genetic links to gay sexual orientation.


Using DNA isolated from saliva samples, the study compared the genomes in 47 pairs of identical twins, yielding the five regions linked to sexual orientation.

Using only that information, researchers could pick out sexual orientation differences in identical twins 67 percent of the time, something that hasn’t been done before, Ngun said.

Ngun said the study isn’t meant to find a “cure” or treatment for being gay, but as a scientific study into the factors influencing sexual orientation. Ngun performed the study as a postdoctoral researcher at the David Geffen School of Medicine at UC Los Angeles. He is now leaving to find a job in the biomedical industry.

Evidence for genetic effects on sexual orientation has been found in other animals, such as fruit flies and in a study released Thursday, the nematode C. elegans. However, the genetic links uncovered in such studies are much more dramatic than the more subtle correlations observed in people.


A structural brain difference in heterosexual and homosexual men was proposed in a 1991 article in the journal Science by openly gay researcher Simon LeVay, then at the Salk Institute for Biological Studies. The study found that a portion of the hypothalamus was more than twice as large in heterosexual men as in homosexual men or women. Other researchers questioned its accuracy. LeVay himself said the study didn’t locate a “gay nucleus”, but one difference out of several.

DNA tools

LeVay wrote just as the boom in genetic sequencing was beginning, and that new tool was employed to examine possible genetic origins of sexual orientation. In the mid-1990s, researcher Dean Hamer identified a band of the X chromosome called Xq28 as holding genetic variants linked to male homosexuality. But other prominent scientists said the evidence falls short of rigorous proof, and a recent followup study has failed to settle the issue.

Ngun and colleagues decided to look at another characteristic of DNA, which determines whether genes are turned on or off. This process is called methylation. The effects of methylation are referred to as epigenetic, because they don’t change the underlying genetic sequence.


A DNA molecule that is methylated on both strands on the center of cytosine. DNA methylation plays an important role for epigenetic gene regulation in development and cancer. ( / Christoph Bock, Max Planck Institute for Informatics)

To find these epigenetic changes, the team studied identical twins, who share the same DNA sequences, to compare methylation patterns. Participating were 37 pairs of twins in which one identified as homosexual and one as heterosexual, and 10 pairs in which both were homosexual. Their epigenetic data was analyzed by an algorithm called FuzzyForest to find areas linked with sexual orientation.

FuzzyForest originally identified nine stretches of the genome correlated with sexual orientation. This has since been narrowed to five areas, Ngun said. The predictive power of these regions is now being tested in a more general population of men, Ngun said.

To confirm the algorithm’s results were really predictive, and not a fluke, “we took that model and gave it data it hadn’t seen before,” from the twins, Ngun said.


The model’s predictions that an individual was gay were more accurate than predictions the person was straight, he said. The reason for that isn’t clear. Predictions about gay men were right 83 percent of the time, while predictions about straight men were accurate only 50 percent of the time.

The findings help make sense of previous genetic research that has yielded inconsistent results, Ngun said. Methylation is used for activating or deactivating some mammalian genes in a characteristic pattern, depending on whether they were inherited from the mother or father. This process is called imprinting. Researchers have found that an area of the genome called 10q26 is linked to sexual orientation only when inherited from the mother. This region is imprinted.

So if the study is correct, both genetic and epigenetic variations contribute to influencing sexual orientation.

Researchers contacted by Genetic Expert News Service gave mixed reviews to the study.


“Note that this is not the same as finding that specific epigenetic marks are causing differences in sexual orientation,” said Christopher Gregg, Assistant Professor of Neurobiology & Anatomy and Human Genetics at the University of Utah. “Thus, the authors’ claim that they have “new insights into the biological underpinnings of sexual orientation” appears to be overstated. The observed differences in epigenetic marks could arise as a consequence of the unknown biological factors that cause heterosexual versus homosexual behaviors, or due to lifestyle differences.”

This Friday, Oct. 8, 2010 photo shows high school senior student Isaiah Baiseri, middle, as he poses for a photo with his parents Russell, left, and Yvette Baiseri at their home in Glendora, Calif. Baiseri heads a gay-straight alliance group at his high school. Baiseri says he started to realize he was gay when he was 11, in the 6th grade. (AP Photo/Damian Dovarganes) ( / AP)

Peng Jin, a professor of human genetics at Emory University in Atlanta, said the study didn’t examine enough people to draw firm conclusions.

“At best the authors could only claim the potential association, but not predicting power,” Jin said.


Margaret M. McCarthy, a professor of pharmacology at the University of Maryland School of Medicine, who studies the relationship between gender and the developing brain, gave a more positive assessment.

“This study provides a major step forward in our understanding of how the brain can be affected by factors outside of the genome,” McCarthy said. “It is also possible that the experience of being a homosexual or a heterosexual has itself impacted the epigenetic profile. But regardless of when, or even how, these epigenetic changes occur, their findings demonstrates a biological basis to partner preference.”

Making sense of evidence

Ngun said the study was prompted by evidence over the years that epigenetic factors help determine whether someone is gay or straight. Besides the imprinted 10q26 region, it’s long been known that the odds of a woman’s son next son being gay increase by 33 percent with each older brother. (The number of older sisters doesn’t change the odds).


Ngun, who is openly gay, said his research into sexual orientation and genetics was prompted by curiosity about himself and others.

“I got into genetics because I found out it’s really fun,” Ngun said. “It’s a big logic puzzle in some ways and I love figuring out what makes people tick. I went into sexual orientation research because I’m self interested I guess, ha ha. I wanted to know what made me the way I am.”

And this is not Ngun’s first look at role of epigenetics.

“Taken together, the evidence strongly suggests a role of epigenetic mechanisms in the regulation of sexual orientation,” Ngun and colleagues wrote in a study presented at the 2014 convention of the American Society of Human Genetics.


That study found orientation-linked areas of the genome, but didn’t present a predictive model, as does this year’s study.

Women were not included in the study because there’s relatively little research on the genetics of female sexual orientation to build on, Ngun said.

“Personally, I think it’s because historically, most scientists were men,” Ngun said. “Therefore, they were interested in themselves.”

“It’s starting to change a little bit,” Ngun said. “There was a study earlier this year, one of the first to really look at whether genetics are involved in sexual orientation in women.”


It may not be possible to boost the study’s predictive power based on just DNA methylation, Ngun said. So other aspects of the genome will need to be considered.

“We’re just looking at a small part of the overall picture,” he said.