Genetic apps: raising more questions than they answer?
Authors: Talha Burki
Journal: The Lancet Digital Health (2019)

The roots of the controversy over Joel Bellenson's app, which provides a score for one's genetic predisposition for same-sex sexual orientation, lie in a research paper published in Science in August 2019. The investigators analysed the DNA of almost 500 000 individuals from the UK Biobank and 23andMe, a company which provides direct-to-consumer genetic testing. The aim was to outline the genetic basis of sexual orientation. The results indicated that 8–25% of same-sex sexual behaviour is attributable to thousands of genetic variants. “Many uncertainties remain to be explored, including how sociocultural influences on sexual preference might interact with genetic influences”, the authors concluded. The research soon came to the attention of Bellenson, an American entrepreneur who is based in Uganda, where homosexual sex is illegal. The Science paper was titled, Large-scale genome-wide association study reveals insights into the genetic architecture of same-sex sexual behaviour. For his app, Bellenson went for, How gay are you? It was released on GenePlaza, a marketplace for genetic apps co-founded by Alain Coletta. Users upload their genetic data to the site and can access a range of apps that interpret this information. The apps can be purchased for a few Euros each. Several of the research team for the Science paper were from the Broad Institute of MIT and Harvard (Cambridge, Massachusetts, USA). At the time, Joseph Vitti was a postdoctoral researcher in genomics at the same establishment. Vitti started a petition against the app, which contributed to its eventual removal from the GenePlaza website. “I struggle to understand the motivations behind a genome-wide association study on non-heterosexual behaviour”, Vitti wrote in a statement on the institute's website, which was part of a debate that the Broad Institute hosted after the publication of the Science paper. He worried that the benefits of the study were outweighed by its potential for harm. Benjamin Neale, who is openly gay, co-authored the Science paper. “The UK Biobank data were available for research through a controlled access process. This meant that it was inevitable someone would pursue studies of same-sex sexual behaviour”, wrote Neale on the Broad Institute's website. The researchers organised workshops to discuss the ramifications of their findings with members of the public and activists. Bellenson's app worried Vitti. “If there is some kind of genetic ‘diagnostic’ or ‘litmus test’ out there for someone's sexuality, it will inevitably become something that is deployed against LGBTQI people in places where they lack protection”, he told The Lancet Digital Health. Vitti's petition requested that GenePlaza remove the How gay are you app “in order to protect vulnerable people in Uganda and worldwide”. Separately, Neale wrote to GenePlaza, urging them to take down the app or, failing that, make it clear that it had nothing to do with his research team. “The ‘score’ you are marketing through this app is a total misrepresentation of the conclusions of the work”, he wrote. “Our study indicated that individual-level prediction is impossible for same-sex sexual behaviour. The promotion of this app and, in particular, the claims it makes are a gross and dangerous mischaracterisation of our work. In our manuscript we explicitly state that ‘these scores could not be used to accurately predict sexual behaviour in an individual.’” In response, Bellenson inserted an additional disclaimer, and changed the app's name to 122 shades of grey, a reference to the number of genetic variants that the app took into account. But Coletta was starting to feel uncomfortable with the negative attention. “We were being framed as persecuting minorities, and that is not an easy thing to hear”, he explained. He took down the app on October, 2019, leaving in its place an essay by Bellenson. At the time of writing, there were fourteen apps available from GenePlaza. They included an app on health traits, an ethnicity calculator, an app that calculates users genetic risk of depression, and an app on coffee metabolism. With the exception of the ethnicity calculator, they are all accompanied by a disclaimer: “this application is not a diagnosis, a prediction, or a predisposition score. This app simply shows what your score would have been if you had participated in this study”. Coletta points out that Bellenson's app was always accompanied by a similar disclaimer. He adds that the data and techniques necessary to run studies such as Neale's are already out there. “The study on which the app was based took data from people who did not know they would be part of that specific research, and yet the authors are telling us they do not want people who sign up for the app to know their own results”, Coletta told The Lancet Digital Health. Bellenson dismisses as absurd the notion that the Ugandan police would go to the trouble of analysing the DNA of those they suspect to be engaging in same-sex sexual activity. “They could get the information they needed far faster by looking at Twitter, FaceBook, and Instagram”, he said. He contends that showing that homosexuality has a genetic component could help improve the situation in Uganda. Yoweri Museveni, Uganda's president since 1986, has previously hinted that he would reconsider the statutes criminalising homosexuality were it to be proven that “indeed, there are people who are born homosexual”. GenePlaza also hosts an intelligence app. Linking intelligence with genetics has a toxic history, but Coletta argues that as long as the data remains exclusively in the hands of the user, there is no reason not to explore the subject. In keeping with this ethos, GenePlaza does not include any apps that allow people to find relatives. “We do not want algorithms that will report other people's data”, said Coletta. “But if you take the decision to obtain your DNA data, then what you choose to do with it should be up to you. In those circumstances, regulation is not the right word, it is more about people pressing for censorship.” For Coletta, the crucial issue is privacy. “No one has access to our data, and that includes the app developers themselves”, he said. Debra Mathews (Johns Hopkins Berman Institute of Bioethics, Baltimore, MD, USA) believes this is not adequate. “Even if the app is not collecting data, we are still talking about a vulnerable, stigmatised group in a country where the behaviour of that group is illegal”, she explained. Mathews points out that apps that interpret people's genetic data should be very careful as to how they convey their results. “For most complex behavioural traits, the contribution of genetics is so small, it really is not the thing we should be focusing on”, she said. “Take something like education attainment; that is completely correlated with where you live and your family income. Those factors are going to have far more explanatory power than anything in your DNA.” She added that people do not always find it easy to interpret probabilities. “If you tell someone they have a 2% chance of death, that sounds completely different to a 98% chance of being fine”, Mathews told The Lancet Digital Health. “Genetics is an incredibly complicated field, and even geneticists do not understand what most of the genome does.” Mathews believes that the absence of regulatory oversight is problematic. “We have not had structures for thinking about these apps as medical devices in a way that would actually lead to their being regulated”, she said. “I am concerned about apps and companies that are not transparent about the fact that people's data are the product.” Coletta stresses that GenePlaza “do not monetise our data, or use it for research, or share it, or sell it”. But this is not the case for other apps. “Are consumers aware that their data is the product for many of these apps?”, asks Mathews. “I worry about the privacy and confidentiality of the data and the lack of scientific support for the kinds of analysis that are being offered.” Mathews notes that researchers have to be very clear with their participants over what is going to happen to their data. “We have to obtain informed consent from whomever is participating in the study; it is not perfect but at least it is all written down and people are given the opportunity to look at what is planned and make their own decision about participation”, she explained. The manufacturers of genetic apps are under no obligation to follow these procedures. Moreover, the study which Bellenson drew on for his app did not require ethical oversight from the Institutional Review Board, since the subjects had been de-identified and did not have any contact with the researchers. This raises questions about how to account for the potential harm that the study could have for vulnerable groups who are affected by the findings but were not involved in the research. In any event, the requirements of ethical oversight do not extend to commercial apps. Bellenson stresses the importance of making bioinformatics fun. But Mathews counters that this can be done without blundering into situations which could harm vulnerable communities. “It is great to want to get people more engaged in genetics”, she said. “But apps like ‘how gay are you’ are not the right way to do it. Stick to things like earlobes or what happens when you eat asparagus. If you claim to assess same-sex attraction, it is going to be bad for the consumer and bad for science.” Vitti agrees. “If we put out these genetic crystal balls for things like sexuality, intelligence, athletic ability, or propensity for criminality, we are going to obscure far more than we illuminate”, he told The Lancet Digital Health.