GWAS Reveals Five Genetic Variants Associated With Same-Sex Behavior

Affectionate, tender male gay couple hugging on beach

Working in close consultation with advocacy and outreach groups, an international group of researchers has provided the clearest evidence into the genetic underpinnings of same-sex sexual behavior. The results of the large-scale GWAS show that “there is no single gay gene” but that same-sex sexual behavior is linked to a contribution of “many small genetic effects scattered across the genome,” according to Benjamin Neale, PhD, associate professor at Harvard Medical School and senior author on the study.

The team identified five genomic variants that are associated with same-sex sexual behavior while also showing that there is no genomic signature that predicts how a person will behave sexually. The study, “Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior” lays to rest the idea of the “gay gene”, popularized by Dean Hamer who linked homosexuality to a specific region of the X chromosome in a 1993 study.

The large GWAS on 477,522 individuals, published today in Science, found five genetic single nucleotide polymorphisms (SNPs) that are associated with engaging in same-sex sexual behavior. The team analyzed data from the UK Biobank (408,995 individuals aged 40–70) and a cohort from 23andMe (68,527)—largely from the United States. Three smaller datasets were used in the work, including the National Longitudinal Study of Adolescent to Adult Health, Molecular Genetic Study of Sexual Orientation, and The Child and Adolescent Twin Study in Sweden.

The primary phenotype examined was whether a person had sex—even one encounter—with someone of the same sex. This information was taken from self-reported responses. UK Biobank participants were asked, “Have you ever had sex with someone of the same sex?” whereas 23andMe participants filled out a “Sexual Orientation Survey” that included questions about sexual identity, sexual attraction, sexual experience, and sexual fantasies.

From there, the team analyzed other phenotypes including, if you had same-sex behavior, what proportion of your total partners have been same-sex? This, according to Jeremy Yoder, PhD, an assistant professor in biology at California State University, Northridge, was a smart design choice because, “genetically, those turn out to be two different things.”

The authors note that the five genetic variants together account for less than one percent of the variation. And, all genetic variants tested accounted for 8 to 25% of variation in same-sex behavior. This reported value, the narrow-sense heritability (h2) is, as explained by Yoder, “the proportion of the variation among people [whether they have had same-sex sexual encounters] that is explained by genetics.” Typically, Yoder notes, it is assumed that the h2 is variance explained by genetics—with everything else explained by the environment.

Andrea Ganna, PhD, a fellow in the Neale lab and first author on the paper notes that, despite the small effect, this genetic variance could hint at some biological pathways that may be involved in same-sex sexual behavior. For example, one SNP is in an area of the genome where genes related to olfaction are located. And, as smell and sexual attraction have been linked, this may lead to a tie to sexual behavior. Another SNP was associated with male baldness (and near the gene TCF12)introducing the role of sex hormones regulation.

But, these hypotheses based on SNP locations are nothing more than speculation, and how these five genetic variants, and the rest of the genome, contribute to same-sex sexual behavior will take many years to uncover. This study “raises more questions than it answers,” notes Laura Hercher, director of research for human genetics at Sarah Lawrence College. She adds that “the most important takeaway of the work is that you cannot simplify the conclusions because complexity is the message.”

“Effectively impossible” to predict sexual behavior from the genome

This is “a really treacherous trait to be dealing with,” notes Yoder. The argument of “born this way,” Yoder tells GEN, took decades to adopt and has served as a cornerstone of the gay community, leading to gay rights, including marriage equality. Hercher agrees, adding that there is a “weird dual set of implications” to link genetics and same-sex behavior. A genetic basis proves that it isn’t a choice, she explains, but also raises the very scary prospect that it could be used as a eugenic measure to avoid homosexuality.

But, Neale asserts that it is “effectively impossible” to predict an individual’s sexual behavior from their genome. Genetics may be an important contributing factor, but it is “less than half of this story for sexual behavior.” He notes that the information here is not enough to make a polygenic risk score. Indeed, the researchers performed a cross-prediction test in the study that was unsuccessful in efforts to explain variation.

The study also has limitations, many of which are common to GWAS studies in general. For example, the sample lacks diversity, with people almost entirely from European ancestry and from a western cultural context. Another limitation is the year of birth of the people involved. For example, the participants born in the 1950s and 60s may have not had a same-sex sexual experience for societal reasons.

Why study this?  

“The risks of this kind of study are really about what happens with the results after they’re published,” notes Yoder. And, it’s very challenging for researchers to do the work and then prevent those bad possibilities from coming to pass.

“It’s one thing to say that, in a twin study, there is a genetic effect,” notes Yoder. It’s a very different thing to say “these are the genes that seem to be involved.” Given the hazardous ways that society could potentially use results like these, is it wise to publish the standard identifiers for the five SNPs that they found?

“Doing science to learn about ourselves is a feature of what, I think, motivates a lot of us to be scientists,” notes Neale. Fah Sathirapongsasuti, PhD, a senior computational biologist at 23andMe, said that 23andMe felt an “obligation” to participate in this research because this topic was one of the top requests that they received from customers as an area to study.

Neale explains further that the data are publicly available and “there were groups indicating that they were going to pursue this line of research.” So, he explains that they wanted to do it first, “in as rigorous and scientifically responsible way as possible.” By aligning with advocacy groups on “what we were doing, how we were doing it” they consulted on how to communicate this information in a way that is as sensitive as possible to the individuals who might be affected by the results. For example, Neale explains that they “rewrote major sections of the paper” to emphasize that the primary focus of the paper is on behavior—not identity or orientation. They also built a website to explain many aspects of their work, including the participants, funding, and results.

“How we did [the study] matters as much as anything else,” notes Neale. Engaging in the advocacy work was a responsibility, given the opportunity to strengthen the case for diversity in the genetic analysis and in the world. The team anticipated how their results could be misunderstood or misinterpreted—and are doing everything they can to head that off.

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