'Gay test' fear mustn't derail work on sexuality's genetic basis

By Dean Hamer The idea of testing someone’s DNA to determine whether they are gay or straight is provocative. So it was no surprise that a recent study by Tuck Ngun at the University of California, Los Angeles, entitled “A novel predictive model of sexual orientation using epigenetic markers“, caused a stir. Talk of a possible test is unhelpful. As a scientist long interested in the role of the genome in human sexuality, I am more intrigued by what the study can tell us about the influence of epigenetic imprinting – the silencing of genes by methylation of DNA. This chemical imprint is passed from parent to child and has implications for a variety of complex human traits. My lab proposed 12 years ago that it plays a role in sexuality. To understand what all the fuss is about now, it’s essential to know some history. The first DNA markers for sexual orientation were reported by my laboratory in 1993, when we discovered an area on the X chromosome – Xq28 – that influences sexuality in gay brothers. This year, that finding was robustly confirmed in a study 10 times the size of our original, which also found an area on chromosome 8 that plays a role. Despite these so-called linkage studies, it was clear that inherited differences in DNA could not account for all of the observed variation in sexual orientation. That led me and graduate student Sven Bocklandt to hypothesise in 2003 that an additional mechanism might be involved: epigenetics. We illustrated the idea by suggesting how atypical imprinting of the X chromosome could lead to failure to inactivate certain genes or activate others, thereby leading to same-sex attraction in males. Although we couldn’t test this directly at the time, some supporting evidence emerged when the X chromosome DNA methylation patterns of the mothers of gay men were compared with those seen in the mothers of straight men. When Bocklandt left for a postdoctoral position with Eric Vilain at UCLA, another author on Ngun’s study, he proposed testing imprinting directly by comparing the methylomes – the entire genome’s epigenetic marks – from pairs of male identical twins in which one is gay and one straight. Despite scepticism from funders, Bocklandt and Vilain persisted, and began recruiting such pairs and analysing their DNA in a way that allowed comparison of some 30,000 methylation sites. Several intriguing correlations were found, but none of them held up to replication. Ngun’s innovation was to expand the search to the entire genome using a new technology that covers a whopping 4 million potential methylation points. These were finally narrowed down to 140,000 points that were compared in 37 gay/straight twin pairs – a small sample for such a complex analysis. Ultimately five sites were identified which, in combination, could be used to classify the sexual orientation of the twins with 67 per cent accuracy. Ngun submitted an abstract describing his preliminary data to the American Society of Human Genetics, hoping to get feedback and ideas for further testing from colleagues at its annual conference last week. This is a standard practice, and Ngun had presented the same data at previous meetings without fanfare. The society’s press office then issued its own release about the work and circulated it to major media outlets. Not surprisingly, there were soon headlines about the new “gay gene test”. Some speculated that the research would lead to abuses, including the elimination of homosexuality through abortion. Underlying the coverage were misconceptions about the research that need correcting. Firstly, it does not amount to a sexual orientation test. Even if the data can be replicated in more twins with highly correlated methylation patterns, the methodology is unlikely to work in unrelated members of the general population. What’s more, the study doesn’t discount the previous linkage results. There is plenty of room for both genes and imprinting, and in fact they may synergise. That means the epigenetic differences, which are by themselves small, may make a difference only when combined with a particular genetic background. Finally, such work will not lead to increased homophobia. Scientific knowledge is one of the best defences against the prejudice that underlies discrimination. As I noted in a recent editorial, surveys show that people who understand the role of biology in sexuality are much more likely to be accepting and inclusive. I hope that Ngun’s preliminary findings will stimulate more research. My fear is that the unnecessary furore stirred up by the press release will inhibit it. That would be a pity, because sexual orientation is one of the most fundamental and fascinating variations in humanity that we can study. (Image credit: George Panagakis/Pacific Press/LightRocket via Getty) More on these topics:
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