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Science

There’s (Still) No Gay Gene

8.29.19

Computer artwork of an autoradiogram of DNA sequences.

Computer artwork by Alfred Pasieka/Science Source


Computer artwork by Alfred Pasieka/Science Source

There is no one gene for being gay, and though genes seem to play a role in determining sexual orientation and same-sex behavior, it’s small, complex, and anything but deterministic. That’s the conclusion of a paper by an international team of researchers, co-led by Benjamin Neale of the Broad Institute of Harvard and MIT, published today in the journal Science. The team combed the genomes of more than 470,000 people in the United States and the United Kingdom to see how genetic variants at millions of different places in the genome correlate with whether participants had ever had sex with someone of the same sex. The study, by far the largest such investigation of sexuality to date, was made possible by combining genetic and behavioral data from more than 400,000 people from the UK’s BioBank study, and from 70,000 customers of the genetic testing company 23andMe, who opted in to having their data used for research.

The researchers found five genetic variants—changes at a single site in the DNA sequence—that correlated with same-sex sexual behavior: two of these had a significant effect only in males, and one only in females. 

The effect of each variant is small and inconsistent: for example, the authors note that in one of the male-specific variants, subjects who had a thymine molecule (“T”) at a particular spot in the genetic sequence on chromosome 11 have a 3.6 percent likelihood of having had sex with other males, while subjects who had a guanine molecule (“G”) there had a likelihood of 4 percent. The other four significant variants (on chromosomes 4, 7, 12, and 15) showed similar, or even smaller, effects.

“It’s effectively impossible to predict an individual’s sexual behavior from their genome,” said Neale, the director of genetics in the Stanley Center for Psychiatric Research at the Broad and an associate professor in medicine at Harvard Medical School (HMS), during a Tuesday teleconference introducing the paper’s findings. In fact, the team estimated that the genetic variants they studied could predict, at best, somewhere between 8 percent and 25 percent of the reported variation in the entire cohort’s sexual behavior. (The idea that a binary variable—i.e., whether a male has or has not had sex with another male—might itself have a “variation” may seem counterintuitive, but this number is analogous to estimating that 50 percent of the variation in a certain population’s height can be attributed to genes—it refers to the differences within the population, not the genetic contribution to any individual’s traits). The rest comes down to the expansive realm of “non-genetic” or “environmental” effects—which Neale said “can range from anything in utero all the way through to who you happen to stand next to on the Tube in the morning.”

Though the genetic effects are small and their provenance uncertain, Neale continued during the press conference, the results do show that genes have a role to play in the development of sexual behavior. “There is no single gay gene, but rather the contribution of many small genetic effects scattered across the genome,” he emphasized. 

Though it’s not clear how any of the five significant genetic variants the study pointed to might act, some leave tantalizing hints at the biology of sexual attraction: one of the male-only variants, for instance, is associated with hormone-related effects like male-pattern baldness and testosterone metabolism, while another is associated with several genes affecting the sense of smell. “We know that smell has a strong tie to sexual attractionbut its links to sexual behaviors are not clear,” said co-author Andrea Ganna, an instructor at HMS and Massachusetts General Hospital from the Institute for Molecular Medicine Finland.

 

The study is in part a response to gay, lesbian, and bisexual people’s curiosity about themselves, said Fah Sathirapongsasuti, a senior scientist at 23andMe and co-author on the study, who is himself gay. “I remember as a teenager trying to understand myself—understand my sexuality. I looked on the Internet for the ‘gay gene.’” Today, he noted, research and information about sex and sexuality is among the categories most requested by 23andMe’s customers. 

Sathirapongsasuti wasn’t the only one looking to the putative “gay gene” for self-understanding or validation. Michael Bronski, professor of the practice in media and activism within the committee on studies of women, gender, and sexuality, and author of A Queer History of the United States, says the allure of a “gay gene” grew from the flourishing gay-rights movement in the decade after the Stonewall riots in 1969. Conservative opponents of the movement claimed that “homosexual acts are a choice, people choose to commit them, or people are seduced into the gay lifestyle,” he explains. The clear counter was a refrain that still echoes today: “Born this way.”

In 1993, Michael Hamer, Ph.D. ’77, then a researcher at the National Institutes of Health, published results showing a correlation between male homosexual behavior and a cluster of genes, called Xq28, at the tip of the X chromosome. Exactly which gene in this cluster may be involved has proven elusive—the current study found no significant association between the X chromosome and same-sex sexual behavior—but the idea that a “gay gene” might lie somewhere in Xq28—or elsewhere—was captivating. Genetics was gaining increasing authority and public attention (the human genome project launched in 1990), Bronski points out, “So ‘I was born this way’ then became a genetic argument, that there is…something physical…that made you have these attractions.” 

Neale’s team places the new study’s conclusions squarely within the tradition of using genetics to embrace human variation: “This is all consistent with this diversity being a key feature of our sexual behavior as a species,” he said during the teleconference. Zeke Stokes, chief programs officer of the LGBTQ advocacy organization GLAAD, concurred in an emailed statement: “This new study provides even more evidence that being gay or lesbian is a natural part of human life, a conclusion that has been drawn by researchers and scientists time and again.”

 

Not everyone has embraced the approach of legitimizing homosexuality through genetics, however. “There are people who say it doesn’t matter,” that their rights shouldn’t depend on biochemistry, says Bronski. Others have warned that the search for a genetic cause would pathologize homosexuality in the same way psychology did in the twentieth century: efforts by psychoanalysts such as Irving Bieber led to the inclusion of homosexuality in the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders until 1972. 

In part because of this contentious history, said Neale, the study’s authors made an effort to engage with activists and advocates within the LGBTQ-rights movement, including GLAAD, using this feedback to adjust how they carried out their analysis and presented their work. A major focus of these discussions, he added, was the distinction between having sex with others of the same sex, and being attracted to them or identifying as non-heterosexual: a bisexual woman, for example, may only ever have had sex with men, while a man who identifies as straight may nevertheless have sex with other men. If the genes identified in the study play a direct causal role at all, said Neale, it may in fact be because they’re related to sexual attraction—but they could also act by making their possessors more open to new experiences in general, or more willing to risk doing something that’s still stigmatized in many places. 

“We re-wrote major sections [of the paper] to emphasize that the primary focus…is on behavior, not on identity or orientation,” he continued. The researchers also took pains to emphasize that nobody should, or indeed could, predict someone’s behavior based on their results.

Another caveat: the study covered only people with European ancestries, meaning that its results probably aren’t reflected in other populations, said Neale. As noted above, the genes that correlated with same-sex sexual behavior also correlated with willingness to take risks, a connection that might not hold up in cultures where homosexuality is less stigmatized and those who are less risk tolerant would therefore feel more able to act openly. And in the case of subjects with a different genetic ancestry, in the context of different genes, the variants this study identified might not matter at all.

“That 8 to 25 percent number” (describing how much of the difference in sexual behaviors is caused by the genetic variants), said Neale, “is really an estimate restricted to the population that we are studying. It is not necessarily a global statement about everyone.” Asked during the teleconference what it might be in other populations, he responded, “We simply don’t know.”

 

A lot remains unknown, even after 51 researchers in six countries, working with the genomes of nearly a half-million people, have announced that a handful of genes have something very small to do with same-sex behavior, at least in white Britons and Americans.

For Bronski, all this effort raises the issue of “Why is this even a question? And why are you doing this research? The genetic part of it, even if there are things people can discover, seems to me to be a minute aspect of the complexity of how people are sexual…It seems to me like doing an analysis of a great novel like Anna Karenina and focusing on the commas and periods rather than the themes.”

While acknowledging that genetics plays only a small part in determining behavior, Neale said that the genetic questions his team explored are important to ask—in part simply because someone will ask them, and the risk of misinterpreting or misapplying the results of such research is high. “The data that made this study possible are publicly available,” he explained. “It’s important that we do this kind of work in as rigorous and scientifically responsible a way as possible.”

That responsibility includes acknowledging not only the multiple non-Caucasian groups the study didn’tcover, but also the groups it couldn’t cover: to avoid confounding variables, the research didn’t include data from intersex or transgender people, and from others whose chromosomal sex differed from their self-identified gender. “This is an important limitation of our analyses,” the authors state in the paper, adding, “We hope that this limitation will be addressed in future work.” 

Another reason the work will continue, said Sathirapongsasuti, is that 23andMe customers and others continue to show interest in learning more about themselves. The company, he said, sees “participating in this…not only as an opportunity to advance research, but as an obligation for us.”

 

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