Not quite five years ago, a collaboration led by researchers at the Broad Institute published what seemed like the last word in “born this way”: a genomic study of same-sex sexual behavior in a cohort of almost half a million people. That project promised to provide, finally, a window into the evolution of human sexual diversity. It demonstrated, about as clearly as we can demonstrate for any behavioral trait, that some element of sexual orientation is inborn — and that the genetic variation underlying human sexual diversity is deeply woven into the history of our species.
Five years later, in the U.S., we’re facing an ongoing wave of state legislation against basic aspects of queer life and culture, from bans on gender-affirming medical care to restrictions targeting drag performances and history lessons. Worldwide, we’ve seen renewed action against sexual and gender minorities, up to and including the imposition of the death penalty for “aggravated homosexuality.” We’ve long thought legal protections for sexual and gender diversity flowed logically from the idea that sexual orientation and gender identity are deeply inborn and immutable, in the way that most people understand genetics — so why didn’t a modern genome-wide association study in the pages of Science move the needle?
Whether or not same-sex attraction and trans gender modality are “genetic” has probably been a point of discussion since Western society first started to wrap its collective head around the very concepts. We tend to think inherited traits are immutable in ways that other traits are not — though any geneticist will tell you that this is really not the case. Height, for instance: I stand five foot eight inches tall on a good day, and this is at one and the same time an essentially fixed feature of my body, the product of the specific genetic code I inherited from my parents, and heavily determined by the quality of care and resources they were able to give me as I grew. A trait may also be entirely non-genetic and yet such a deep part of a person’s identity that it would be cruel to make them change it — no gene determined that my first language would be English, but requiring me to use only Mandarin in daily life would be a comedy of errors at best.
If the genetics of sexuality and gender identity are more nuanced than they might seem, the evolution of those traits are still more complex. A naive “evolutionary” perspective on same-sex orientation might be that genetic variants promoting same-sex attraction should be eliminated from the human population in a few generations. But that’s a deeply simplistic view of natural selection. Gene variants for same-sex attraction could persist if they affect other traits — a phenomenon we call “pleiotropy” — that offset a lack of interest in direct reproduction: variants that promote same-sex attraction in men could improve fertility when carried by women, for instance. They could also persist via kin selection if same-sex oriented people have, historically, helped their close relatives raise more children.
If more than one genetic locus shapes sexual orientation, the math gets even better for same-sex variants: Say there are ten loci across the genome with small effects on orientation, and only people with “same-sex” variants at all ten loci develop same-sex attraction. There might be lots of people carrying same-sex variants, then, who never develop same-sex attraction because they don’t have the full set. The more loci there are involved, the smaller their individual contributions, and the weaker would be selection’s power to remove same-sex variants at those loci. This “polygenic” model of sexual orientation works out even if there’s no pleiotropy or kin selection, though it could be true alongside either both of those scenarios, too.
All of that was pure speculation before we knew whether any genes contributed to same-sex orientation, much less how many. Studies of twins have provided indirect evidence for genetics, without identifying specific genes; a small study published in 1993 found an association between same-sex orientation in men and genetic variants on the X chromosome, but this pattern wasn’t consistently replicated in followup studies. [Edited to add: Actually, a 2021 meta-analysis using data from multiple participant panels does recover significant associations in this region.]
Even as advancing DNA sequencing technology made it possible to read more of the genome in larger and larger study cohorts, no modern study addressed sexual orientation. Despite the popular interest in the question, sexual orientation and gender identity were not, I think, a priority for big genetic studies because, first, they’re not disease traits like breast cancer or schizophrenia; and, second, they’re much more difficult to measure than a trait like height. People’s understanding of their orientation and gender identity changes over time, and they may not express these identities freely if they live in a community that doesn’t accept homosexuality or transgender identity — or, indeed, actively persecutes sexual and gender minorities.
That changed with the study released in 2019. The authors, led by MIT Broad’s Andrea Ganna, assembled data from 477,522 members of the U.K. Biobank cohort and customers of the 23andMe personal genomics service. Ganna et al. used this data in a genome-wide association study, systematically scanning through loci in the genome, and, at each locus, testing whether participants who reported having had same-sex sexual experiences were more likely to carry one variant or another. Across hundreds of thousands of loci, five had statistically significant associations between variants and same-sex experience.
The effect sizes of the associations at those five loci were tiny, however. For the locus with the sharpest difference between people with and without non-heterosexual experiences, men carrying one variant were 10% more likely to report at least one same-sex experience than men carrying the other variant. As I penciled out back when the study was first published, if 4% of the population has same-sex orientation (as is estimated for the U.S.), that means for every 1,000 men carrying the “gay” variant at this locus, about 44 would actually have had same-sex experiences.
This is exactly what we mean by a polygenic trait: many loci make small contributions, many of those contributions so small that people carry them without manifesting the associated trait. Thus, we get a variant “significantly” associated with same-sex sexual experiences which, in 956 out of 1,000 carriers, does not actually result in same-sex sexual experience. This also means that the results may not translate well to human populations outside the U.K. or the 23andMe customer base. Indeed, Ganna et al. tested whether the associations they detected could predict same-sex behavior in two smaller study cohorts, and found that they didn’t. This is a sufficiently big caveat that the authors made note of it in the paper’s abstract.
Reactions to this big new data set were far from uniformly enthusiastic. The study received widespread attention in mainstream media, but reactions in LGBTQ-focused outlets are particularly interesting. Out Magazine noted the study’s failure to parse out gender identity beyond the man/woman binary and zeroed in on the lack of racial diversity in the study cohort; it later ran an in-depth consideration (which, full disclosure, quotes me quite a bit) of possible negative consequences to biological studies of gender identity and sexual orientation. The Advocate carried a critique by Dean Hamer, the lead author of the 1993 study, who pointed out that same-sex sexual behavior isn’t the same as deeply held, self-identified sexual orientation. Hamer has a point: Ganna et al. treated participants who reported even a single same-sex experience as “non-heterosexual”, though these people were not a large fraction of the “non-heterosexual” group, and the authors took some pains to differentiate behavior from orientation in the text.
Then, too, within weeks of the study’s publication, an app developer used its results to construct a “test” that would read a personal genomic sequence of the sort you can get from 23andMe and predict how likely it was that the source of that sequence was gay. This despite the disclaimer against precisely that application in the paper’s abstract. There is, unfortunately, a real history of junk science used to suss out sexual orientation under homophobic governments — and the app’s author was based in Uganda, which has a history of virulently antigay laws, up to the recent imposition of the death penalty. A campaign by concerned geneticists, including some of the paper’s authors, got the app taken down.
Elsewhere, homophobes responded to the GWAS much as they have to decades of twin studies finding genetic contributions to sexual orientation, with something between denial and deliberate misunderstanding. “Even if up to 32 percent of a person’s same-sex sexual behavior is genetically conditioned [an estimate derived from the GWAS study cohort], this means that more than two-thirds of their sexual behavior is not,” wrote one antigay religious conservative. This, of course, misunderstands the relationship between genetics and environment — much less the multitude of deeply inherent features of personal identity that aren’t genetic.
Scientific responses and followups percolated out more slowly. Hamer lead a formal Comment article in Science to get his objections into the peer-reviewed record. In 2021, a Chinese team published a study of sexual orientation in a panel of self-identified homosexual men, with explicit comparison to the 2019 results — and they did find Ganna et al‘s GWAS had some predictive power in their new cohort. Those authors also followed up with biochemical analysis of a brain region linked to one of the candidate loci from their study, and attempted to validate its role in orientation using genetically engineered mice.
(Whether one male mouse “mounting” another male mouse is relevant to human sexual orientation is a question they do not appear to have considered in much depth.)
More interesting, to my mind, than a mouse model of sexual orientation is another 2021 paper that reanalyzed the Ganna et al. GWAS result in light of other human behavioral data. That study found genetic variants associated with same-sex behavior were also associated with having more opposite-sex partners, if they were carried by people who didn’t develop same-sex attraction. This supports a polygenic version of the pleiotropy hypothesis: On the one hand, a majority of people carrying variants associated with same-sex behavior don’t actually develop same-sex attraction, and on the other, those variants are associated with opposite-sex-oriented behavior that could be associated with greater reproductive success.
Strictly on a scientific basis, I think we can say five years later that the big GWAS of same-sex behavior was a moderate success. Its design was less than perfect, but defensible given the data available; and its results have shown at least some degree of replicability. Better yet, the study and its followups narrow down how same-sex orientations have been part of the human evolutionary story.
As I’ve written before, the genetics of orientation and gender identity provide a link to a kind of biological ancestry that queer people rarely enjoy. We’re mostly born to straight, cisgender parents, and we rarely know of direct ancestors who share our identities. The appeal of “gay genes” is much the same as the appeal of finding specific historical figures who had same-sex relationships or gender identities beyond the binary — they show how people like us have always been part of humanity’s story.
As an argument to advance public support for queer rights, though, it’s hard to see a way in which the big GWAS helped.
Before it was published, I think a lot of us expected that robust data linking specific genes to orientation would be a strong argument for treating LGBTQ identities fairly. Certainly the study’s authors had that expectation. “I didn’t do this to understand myself better, but because better understanding of things like same-sex sexual behavior can lead to stigma reduction,” senior author Benjamin Neale told WBUR at the time.
Because people conflate “genetic” and “innate”, evidence that sexual orientation and gender identity have a genetic basis has generally been seen as giving them a legal footing alongside race and ethnicity. Public approval of same-sex relationships and support for same-sex marriage has indeed risen alongside acceptance of the idea that sexual orientation is at least partially “something a person is born with”, and the U.S. Supreme Court decision requiring legal recognition of same-sex marriages analogized gay and lesbian couples to mixed race couples.
That polling doesn’t provide even an indirect idea as to the study’s impact on public opinion, because Gallup doesn’t appear to have polled whether Americans believe that sexual orientation is “something a person is born with” since 2019. Support for legal recognition of same-sex marriage continued a long-term upward trend, holding at 71% in the last two years polled; agreement that “gay or lesbian relations are morally acceptable” has been more volatile but remains high.
What we have rather than public opinion is the explosion of anti-queer state legislation, and, this month, a rash of stochastic threats and vandalism against Pride celebrations and displays. The legislative push has overwhelmingly targeted trans people and drag performances, topics that are at best indirectly connected to the focus of the 2019 GWAS — though open discussion of gay and lesbian relationships has been one of the targets of book bans and repressive new public school policies. These activities may not reflect majority public opinion, even in the states and school districts where they’re implemented, but they do reflect a resurgent, organized campaign against the very idea that diversity of orientation and gender identity is a natural part of the human story.
A paper in Science cannot stop that kind of political organizing simply by virtue of its existence, no matter how big its sample size or how carefully its results are framed. On this and many other topics, life in 2024 means accepting that public discourse is rarely moved by empirical data. Data may provide us with a story we can tell in opposition to organized hatred, but science, on its own, cannot save us. The lesson of the last five years is an old one, in the history of queer liberation: the only way we can win and keep our place in society is to organize and fight for that place.
If knowing the genetic basis of sexual orientation gives us a glimpse into the history of human sexual diversity, it’s up to us queer people, and our allies, to tell that story — and to use it as ammunition in the fight for our rights.
References
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Futuyma DJ and SJ Risch. 1984. Sexual orientation, sociobiology, and evolution. Journal of Homosexuality. 9:2-3, 157-168. doi: 10.1300/J082v09n02_10
Ganna A, KJH Verweij, MG Nivard, et al. 2019. Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior. Science. 365:eaat7693. doi: 10.1126/science.aat7693
Dean H. Hamer et al. 1993. A linkage between DNA markers on the X chromosome and male sexual orientation. Science 261: 321-327. doi: 10.1126/science.8332896
Hu SH, H-m Li, H Yu, et al. 2021. Discovery of new genetic loci for male sexual orientation in Han population. Cell Discovery. 7:103. doi: 10.1038/s41421-021-00341-7
Sanders AR, GW Beecham, S Guo, JA Badner, S Bocklandt, BS Mustanski, DH Hamer, and ER Martin. 2021. Genome-wide linkage study meta-analysis of male sexual orientation. Annals of Sexual Behavior 50:3371-3375. doi: 10.1007/s10508-021-02035-3
Zietsch BP, MJ Sidari, A Abdellaoui, et al. 2021. Genomic evidence consistent with antagonistic pleiotropy may help explain the evolutionary maintenance of same-sex sexual behaviour in humans. Nature Human Behaviour. 5:1251–1258. doi: 10.1038/s41562-021-01168-8
