New Clues That Sexual Orientation Could Be Epigenetic

Neil Osterweil

October 14, 2015

UPDATED October 16, 2015 // BALTIMORE — An algorithm that incorporates epigenetic information from five regions of the human genome can predict the sexual orientation of males with nearly 70% accuracy, according to results from a new study presented here at the American Society of Human Genetics 2015.

This is the first time researchers have used a biomarker-based model to predict sexual orientation, and the finding is making international headlines.

Still, the team, led by senior investigator Eric Vilain, MD, PhD, director of the Center for Gender-Based Biology from the University of California, Los Angeles, emphasize that the work is preliminary.

"This is about understanding who we are as humans. It's about understanding the mechanisms of desire," Dr Vilain told Medscape Medical News. The findings shed light on the origins of "one of the most pronounced sex differences in the animal kingdom."

His team studied patterns of DNA methylation in identical twins to determine gene-expression levels in disparate regions of the genome. Although the genetic sequences of twins are virtually identical, environmental influences can result in epigenetic changes that can affect DNA methylation and alter gene expression.

The investigators looked at DNA from 37 pairs of identical twins in which one of the siblings identified as homosexual. Ten pairs of twins in which both siblings identified as homosexual served as the control group.

Genomic Sites of Methylation

They identified the genomic sites where methylation took place and consolidated them into short regions on the basis of proximity and their correlation with methylation patterns.

They then applied an algorithm to the data to identify the genomic regions most likely to be relevant to sexual orientation.

They initially identified nine genomic regions, but in the final predictive model, pared those down to the five that turned out to have the highest predictive accuracy, including regions associated with the regulatory domains of the CIITA and KIF1A genes.

CIITA encodes for an activator protein of class II major histocompatibility complex. KIF1A encodes for a transport protein in neurons that is important for shuttling synaptic vesicle precursors along axons.

Using the five loci, the final model had an overall accuracy of 67% (= .03), correctly identifying 50% of men predicted as heterosexual and 83% of men predicted as homosexual.

First evidence of the epigenetic influences on sexual orientation comes from studies showing that identical or monozygotic twin pairs have a high level of discordance for sexual preference, and from the so-called fraternal birth order effect, in which each male pregnancy that a woman has increases the chance that the next son will be gay by 33%, Dr Vilain explained.

In addition, evidence has shown that women who are exposed to androgen early in life are more likely to identify as homosexual or bisexual.

Collectively, these observations support the idea that sexual orientation could have epigenetic origins, he said.

"None of this work should be construed as part of finding a 'cure' for homosexuality," said investigator Tuck Ngun, PhD, also from the University of California, Los Angeles.

However, "no one person can control how information is used," he added. Dr Ngun urged scientists, policy makers, and the general public to work together to ensure that research on sexual orientation, or any potentially genetic or epigenetic trait, for that matter, is not misused.

Social Implications

These findings must be interpreted with caution, said Aleksandar Rajkovic, MD, PhD, from the Magee–Womens Research Institute and Foundation in Pittsburgh, who was not involved with the study.

"Because of the social implications, they can be easy to misinterpret," he said, echoing Dr Ngun's concern.

Dr Ngun acknowledged that the study is limited by the reliance on saliva rather than on neural tissue for analysis, and the fact that the phenotypic assessment involved a small sample.

Dr Rajkovic added that, as the investigators themselves acknowledge, the sample size is small, an opinion shared by session cochair Terrence Furey, PhD, from the University of North Carolina at Chapel Hill.

"As Dr Ngun fully admitted, the study is very underpowered at this point. I think it's suggestive and it will be interesting once they're able to increase the number of individuals to see how well it holds up," Dr Rajkovic told Medscape Medical News.

The study was supported by the Vilain lab. Dr Vilain, Dr Ngun, and Dr Rajkovic have disclosed no relevant financial relationships.

American Society of Human Genetics (ASHG) 2015: Abstract 95. Presented October 8, 2015.

Editor's note: The headline has been edited to specify that this is an epigenetic study.


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