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Epigenetic Markers Predict Male Sexual Orientation

By Australian Science Media Centre

Epigenetic differences between male twins has been used to identify sexual orientation with up to 70% accuracy, according to unpublished results presented at the American Society of Human Genetics 2015 annual meeting.

“The key issue here is that the authors have searched through the entire genome to identify some difference between discordant twins. Given the number of tests, it is likely that some regions will show up as differentiated by chance. Without validation of the result in an independent data set it is not really possible to know whether there is any substance in this claim.”

Prof Gil McVean, Professor of Statistical Genetics, University of Oxford

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“The authors of this abstract utilized a very small number of samples and discovered certain epigenetic markers could be associated with sexual orientation. However, I am not sure whether ‘the predictive model’ as claimed in the abstract is a correct term given the overall sample size. At best the authors could only claim the potential association, but not predicting power.

“It is unclear what tissues they used for epigenetic profiling. Blood DNA is likely the source, which could be the caveat of this study. It has been continuously debated whether the methylation status of blood DNA could be used as epigenetic biomarker for brain-related phenotypes. In addition, additional cytosine modifications have been discovered in recent years and the experimental system used in this study could not distinguish some of these modifications. The interpretation of their results could be limited.

“The observed epigenetic changes, particularly if from blood DNA, unlikely determine the complex behaviors, such as sexual orientation. These observations are potentially intriguing, however, interpreting these results certainly needs caution."

Dr Peng Jin, Professor of Human Genetics, Emory University

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“Epigenetic marks are the consequence of complex interactions between the genetics, development and environment of an individual. Epigenetics is still a young science, and although there is great potential very little is known about the mechanisms that shape the epigenetic landscapes of an individual. Simple correlations – if significant – of epigenetic marks of an individual with anything from favourite football player to disease risk does not imply a causal relationship or understanding.”

Dr Eric Miska, Herchel Smith Chair of Molecular Genetics, The Gurdon Institute and Department of Genetics, University of Cambridge

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“This new study investigates the possibility that specific epigenetic marks on the genome can be used as markers that indicate male heterosexual versus homosexual behavior. Note that this is not the same as finding that specific epigenetic marks are causing differences in sexual orientation. Thus, the authors’ claim that they have ‘new insights into the biological underpinnings of sexual orientation’ appears to be overstated.

“The observed differences in epigenetic marks could arise as a consequence of the unknown biological factors that cause heterosexual versus homosexual behaviors, or due to lifestyle differences. Indeed, epigenetic marks differ between tissues and cells and, although it is not stated, the authors presumably analyzed blood samples from twins, rather than specific regions of the brain that control sexual behaviors and attraction. Therefore, the study does not provide evidence for ‘epigenetic influences on sexual orientation’, but it appears to have identified candidates for further investigation and an epigenetic signature that has some predictive utility in twins.

“Overall, the importance of these findings will hinge on how reproducible they are in future studies that include larger groups of heterosexual and homosexual individuals.”

Dr Christopher Gregg, Assistant Professor of Neurobiology & Anatomy and Human Genetics, University of Utah

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“Studies that associate biomarkers with particular traits are notoriously prone to false-positive results due to the tendency of these studies to find spurious associations that are down to sheer chance. The key test is whether the associations are found in a completely independent study population.

“From the abstract this confirmatory test does not appear to have been performed in this study. Without it, the results should be considered to be suggestive and preliminary but in need of verification before any firm conclusions can be drawn.”

Prof Johnjoe McFadden, Professor of Molecular Genetics, University of Surrey

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“With only a research summary (abstract) to work with it is difficult to give a full appraisal of the research. Nonetheless, to claim a 70% predictive value of something as complex as homosexuality is bold indeed. I wait with baited breath for a full peer-reviewed article.

“While there is strong evidence in general for a biological basis for homosexuality, my personal impression has always been one of a multiple contributory factors, including life experiences. My gut feeling it that, as the complete story unfolds, the association may not be quite as simple as the summary (abstract) and press release suggest. The important thing to note however is the mounting evidence that homosexuality is a perfectly normal trait segregating in human populations.”

Prof Darren Griffin, Professor of Genetics, University of Kent