How genes influence sexual orientation has sparked debate for at least a quarter-century. But geneticists have had only a handful of underpowered studies to address a complex, fraught, and often stigmatized area of human behavior. Now, the largest-ever study of the genetics of sexual orientation has revealed four genetic variants strongly associated with what the researchers call nonheterosexual behavior. Some geneticists are hailing the findings as a cautious but significant step in understanding the role of genes in sexuality. Others question the wisdom of asking the question in the first place.
Andrea Ganna, a research fellow with the Broad Institute in Cambridge, Massachusetts, and Harvard Medical School in Boston, and colleagues examined data from hundreds of thousands of people who provided both DNA and behavioral information to two large genetic surveys, the UK Biobank study and the private genetics firm 23andMe. They analyzed DNA markers from people who answered either “yes” or “no” to the question, “Have you ever had sex with someone of the same sex?” In total, they identified 450,939 people who said their sexual relationships had been exclusively heterosexual and 26,890 people who reported at least one homosexual experience.
In Ganna’s talk yesterday at the annual meeting of the American Society of Human Genetics here, he emphasized that the researchers were cautious about exploring sexual behavior that is still illegal in many countries, and that they tried to frame their questions carefully “to avoid a fishing expedition.” The team, which includes behavioral scientists, preregistered their research design and also met regularly with members of the lesbian, gay, bisexual, transgender, or questioning (LGBTQ) community to discuss and share results. Ganna acknowledged that what they call “nonheterosexual behavior” includes “a large spectrum of sexual experiences, that go from people who engage exclusively in same-sex behavior to those who might have experimented once or twice.”
The researchers performed a genome-wide association study (GWAS) in which they looked for specific variations in DNA that were more common in people who reported at least one same-sex sexual experience. They identified four such variants on chromosomes seven, 11, 12, and 15, respectively.
Two variants were specific to men who reported same-sex sexual experience. One, a cluster of DNA on chromosome 15, has previously been found to predict male-pattern baldness. Another variant on chromosome 11 sits in a region rich with olfactory receptors. Ganna noted that olfaction is thought to play a large role in sexual attraction.
A much smaller 1993 study, which used a different kind of association technique known as a genetic linkage study, had suggested a stretch of DNA on the X chromosome was linked to inherited homosexuality. In the new GWAS, that stretch was not found to be associated with the reported same-sex behavior. But the lead author of the earlier study, Dean Hamer, then of the National Institutes of Health in Bethesda, Maryland, praised the new work. “It's important that attention is finally being paid [to the genetics of sexual orientation] with big sample sizes and solid institutions and people,” he said. “This is exactly the study we would have liked to have done in 1993.”
The four newly identified genetic variants also were correlated with some mood and mental health disorders. Both men and women with the variants were more likely to have experienced major depressive disorder and schizophrenia, and women were more likely to have bipolar disorder. Ganna stressed that these findings should not be taken to mean that the variants cause the disorders. Instead, it “might be because individuals who engaged in nonheterosexual behavior are more likely to be discriminated [against], and are more likely to develop depression,” he said.
Ganna noted that the correlation with schizophrenia and risk-taking behavior was more pronounced in the UK Biobank participants, who tend to skew older than those in the 23andMe group. That could be because older generations faced more sexual discrimination than younger ones, Ganna said, noting that environment likely plays a significant role in which traits wind up correlating with sexual orientation.
Overall, he said the findings reinforce the idea that human sexual behavior is complex and can’t be pinned on any simple constellation of DNA. “I’m pleased to announce there is no ‘gay gene,’” Ganna said. “Rather, ‘nonheterosexuality’ is in part influenced by many tiny genetic effects.” Ganna told Science that researchers have yet to tie the genetic variants to actual genes, and it’s not even clear whether they sit within coding or noncoding stretches of DNA. Trying to pin down exactly what these DNA regions do will be among the team’s difficult next steps.
“It’s an intriguing signal,” he said. “We know almost nothing about the genetics of sexual behavior, so anywhere is a good place to start.”..He added that the four genetic variants could not reliably predict someone’s sexual orientation. “There’s really no predictive power,” he said.
Given the complexity of human sexual behavior, much of which is not captured in the study questions, biomedical informatics graduate student Nicole Ferraro from Stanford University in Palo Alto, California, questioned the work’s utility. She and fellow biomedical sciences grad student Kameron Rodrigues said the study didn’t do enough to explore the nuances of how one’s sexual identity differs from sexual behavior, and they worried that the study could be used to stigmatize members of the LGBTQ community. “It just seems like there’s no benefit that can come from this kind of study, only harm,” Rodrigues said.
The abstract for Ganna’s talk referenced another provocative result: Heterosexual people who possess these same four genetic variants tend to have more sexual partners, suggesting associated genes might confer some mating advantage for heterosexuals. That could help explain why these variants might stick around in populations even if people attracted to the same sex tend to have fewer children than heterosexuals. Ganna did not touch on that finding in his talk, citing lack of time.
That was probably a wise choice, geneticist Chris Cotsapas at the Yale School of Medicine said, because the evolutionary implications haven’t been firmed up. “People are going to oversimplify it to say, ‘Gay genes help straight people have more sex,’ and it’s really not that simple,” he said.
Overall, the findings were “very carefully, cautiously presented,” Cotsapas said, and represent a good start for geneticists charting the complexities of human sexuality.