Massive study concludes that there is no ‘gay gene’

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LGBTThe largest study to date on the genetic basis of sexuality has revealed five spots on the human genome that are linked to same-sex sexual behaviour – but none of the markers are reliable enough to predict someone’s sexuality.

The findings, based on the genomes of nearly 500,000 people, shore up the results of earlier, smaller studies and confirm the suspicions of many scientists: while sexual preferences have a genetic component, no single gene has a large effect on sexual behaviours.

“There is no ‘gay gene’,” says lead study author Andrea Ganna, a geneticist at the Broad Institute of MIT and Harvard University in Cambridge, Massachusetts. Ganna and his colleagues also used the analysis to estimate that up to 25% of sexual behaviour can be explained by genetics, with the rest influenced by environmental and cultural factors – a figure similar to the findings of smaller studies.

“This is a solid study,” says Melinda Mills, a sociologist at the University of Oxford, UK, who studies the genetic basis of reproductive behaviours. But she cautions that the results may not be representative of the overall population – a limitation that the study authors acknowledge. The lion’s share of the genomes comes from the UK Biobank research programme and the consumer-genetics company 23andMe, based in Mountain View, California. The people who contribute their genetic and health information to those databases are predominantly of European ancestry and are on the older side. UK Biobank participants were between 40 and 70 years old when their data were collected, and the median age for people in 23andMe’s database is 51.

The study authors also point out that they followed convention for genetic analyses by dropping from their study people whose biological sex and self-identified gender did not match. As a result, the work doesn’t include sexual and gender minorities (the LGBTQ community) such as transgender people and intersex people.

Scientists have long thought that someone’s genes partly influenced their sexual orientation. Research from the 1990s2 showed that identical twins are more likely to share a sexual orientation than are fraternal twins or adopted siblings. Some studies suggested that a specific part of the X chromosome called the Xq28 region was associated with the sexual orientation of people who were biologically male – although subsequent research cast doubt on those results.

But these studies all had very small sample sizes and most focused on men, says Mills. This hampered scientists’ ability to detect many variants associated with sexual orientation.

In the recent study, Ganna and his colleagues used a method known as a genome-wide association study (GWAS) to look at the genomes of hundreds of thousands of people for single-letter DNA changes called SNPs. If lots of people with a trait in common also share certain SNPs, chances are that the SNPs are related in some way to that characteristic.
The researchers split their study participants into two groups – those who reported having had sex with someone of the same sex, and those who didn’t. Then the researchers performed two separate analyses. In one, they evaluated more than one million SNPs and looked at whether people who had more SNPs in common with each other also reported similar sexual behaviours. The scientists found that genetics could explain 8–25% of the variation in sexual behaviour.

For their second analysis, Ganna and his colleagues wanted to see which particular SNPs were associated with same-sex sexual behaviours, and found five that were more common among those individuals. However, those five SNPs collectively explained less than 1% of the variation in sexual behaviour.

This suggests that there are a lot of genes that influence sexual behaviour, many of which researchers haven’t found yet, says Ganna. An even larger sample size could help to identify those missing variants, he says. But Ganna cautions that these SNPs can’t be used to reliably predict sexual preferences in any individual, because no single gene has a large effect on sexual behaviours.

Although the researchers have identified some of the SNPs involved in same-sex sexual behaviour, they aren’t sure what the genetic variants do. One is near a gene related to smell, which Ganna says has a role in sexual attraction. Another SNP is associated with male-pattern baldness – a trait influenced by levels of sex hormones, which suggests that these hormones are also linked to same-sex sexual behaviour.

The results demonstrate the complexity of human sexuality, says Ganna. They also presented a challenge to the study researchers, who knew that explaining nuanced findings on such a sensitive topic to the general public would be tricky.

To ensure that their results are not misinterpreted, the study researchers worked with LGBTQ advocacy groups and science-communication specialists on the best way to convey their findings in the research paper and to the public. Their efforts included the design of a website that lays out the results – and their limitations – to the public, using sensitive, jargon-free language.

Ewan Birney, a geneticist and director of EMBL European Bioinformatics Institute near Cambridge, UK, applauds that effort. “It’s a communications minefield,” he says. Although some researchers and LGBTQ advocates might question the wisdom of conducting this kind of research, Birney says that it’s important. There has been a lot of sociological research on same-sex sexual behaviours, he says, but this is an incredibly complicated topic. It’s time to bring a strong, biologically based perspective to the discussion, Birney says.

Abstract
Introduction: Across human societies and in both sexes, some 2 to 10% of individuals report engaging in sex with same-sex partners, either exclusively or in addition to sex with opposite-sex partners. Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for the specific genes involved have been underpowered to detect effect sizes realistic for complex traits.
Rationale: For the first time, new large-scale datasets afford sufficient statistical power to identify genetic variants associated with same-sex sexual behavior (ever versus never had a same-sex partner), estimate the proportion of variation in the trait accounted for by all variants in aggregate, estimate the genetic correlation of same-sex sexual behavior with other traits, and probe the biology and complexity of the trait. To these ends, we performed genome-wide association discovery analyses on 477,522 individuals from the United Kingdom and United States, replication analyses in 15,142 individuals from the United States and Sweden, and follow-up analyses using different aspects of sexual preference.
Results: In the discovery samples (UK Biobank and 23andMe), five autosomal loci were significantly associated with same-sex sexual behavior. Follow-up of these loci suggested links to biological pathways that involve sex hormone regulation and olfaction. Three of the loci were significant in a meta-analysis of smaller, independent replication samples. Although only a few loci passed the stringent statistical corrections for genome-wide multiple testing and were replicated in other samples, our analyses show that many loci underlie same-sex sexual behavior in both sexes. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in male and female same-sex sexual behavior, and the genetic influences were positively but imperfectly correlated between the sexes [genetic correlation coefficient (rg)= 0.63; 95% confidence intervals, 0.48 to 0.78]. These aggregate genetic influences partly overlapped with those on a variety of other traits, including externalizing behaviors such as smoking, cannabis use, risk-taking, and the personality trait “openness to experience.” Additional analyses suggested that sexual behavior, attraction, identity, and fantasies are influenced by a similar set of genetic variants (rg > 0.83); however, the genetic effects that differentiate heterosexual from same-sex sexual behavior are not the same as those that differ among nonheterosexuals with lower versus higher proportions of same-sex partners, which suggests that there is no single continuum from opposite-sex to same-sex preference.
Conclusion: Same-sex sexual behavior is influenced by not one or a few genes but many. Overlap with genetic influences on other traits provides insights into the underlying biology of same-sex sexual behavior, and analysis of different aspects of sexual preference underscore its complexity and call into question the validity of bipolar continuum measures such as the Kinsey scale. Nevertheless, many uncertainties remain to be explored, including how sociocultural influences on sexual preference might interact with genetic influences. To help communicate our study to the broader public, we organized workshops in which representatives of the public, activists, and researchers discussed the rationale, results, and implications of our study.

Authors
Andrea Ganna, Karin JH Verweij,Michel G Nivard, Robert Maier, Robbee Wedow, Alexander S Busch, Abdel Abdellaoui, Shengru Guo, J Fah Sathirapongsasuti, 23andMe Research Team, Paul Lichtenstein, Sebastian Lundström, Niklas Långström, Adam Auton, Kathleen Mullan Harris, Gary W Beecham, Eden R Martin, Alan R Sanders, John RB Perry, Benjamin M Neale, Brendan P Zietsch

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