N.E.Whitehead, Ph.D., December 2012
A paper by epigenetic researchers (Rice, W.R., Friberg, U. Gavrilets, 2012) has been generally reported as being a new explanation of homosexuality. My conclusion, in accordance with that of the authors, is that this is a theory only. There have been numerous attempts within at least 13 different research fields to show a strong biological basis to homosexuality and all have failed. This new field – epigenetics – will probably join them. The authors make a good case that epigenetics should be included in the mix of factors contributing to homosexuality. I agree, but believe it will prove to be a minor contributor only, along with many other minor contributors.
Epigenetics is control of genetic expression by factors other than the genes. These factors may be pre-natal or post-natal (occurring at any time of life), often coming from the exterior environment, both biological and social. Epigenetic marks (changes in protein configurations around the DNA) can also be passed on to descendants – but only to some extent.
The paper really discusses sexually dimorphic genitalia, not homosexuality Their theory, reflected in the title of their paper, Homosexuality as a consequence of epigenetically canalized sexual development, is that prenatal epigenetics causes a “canalization” (chanelling) to heterosexuality and also to homosexuality. This is a misleading title for the paper because it predominantly discusses what they believe to be a strong epigenetic influence on sexual differentiation in the genitalia of the two sexes. From this basis they theorise epigenetics must also have a predominant role in homosexuality.
The work relies on the generally accepted idea that prenatal testosterone is critical in sex-development, and the authors believe that epigenetics play an important role in reinforcing the sexual differentiation caused by testosterone., e.g., they make the statement, “ …sexual dimorphism strongly influenced by androgen exposure – both genitalia and brain”. However they do not seem to have encountered the important 2012 paper (Lombardo et al. 2012) in which testosterone is shown to have only a weak influence on sexual dimorphism in the brain (15-20%; Whitehead 2014), see the posting on this site for a review).
Proselytising for epigenetics?
For an illustration of the strength of epigenetic influence they choose one process which appears to be the strongest they can find, one in which the epigenetic marks correlate 0.67 (out of 1.0) with gene expression. This seems strong but the degree of variance (influence) is 0.672, only 0.44, a modest to moderate influence only. It is also a poor example of the canalization they want to apply to homosexuality, because the process they selected has nothing to do with sexual development. If it is intended as an indicator of strength of influence on homosexuality it is a puzzling one, and there is clearly room for many other explanations.
This is an example of a tendency in the paper to elevate various processes to the status of canalization, e.g.,“Strong candidates for canalization”, “potential… to influence”. But all we really have is a suggestion that epigenetics may be involved, and dominant, but their best example is not about sexual differentiation and had no more than a modest to moderate influence.
Their suggestion that epigenetics is dominant is unlikely for the simple reason that genes vary little from generation to generation, but epigenetic marks vary a lot and most do not even survive transfer to immediate offspring. Are we really arguing that such a flimsy and vulnerable system is predominantly responsible for anything in our development - particularly anything which is as rigidly biologically prescribed as the genitalia of the two sexes? A far more robust model for the development of the two sexes would be one in which many separate processes, each minor, converge to give the same result, so that if one process is knocked out by some biological accident, the process as a whole would still survive. A priori, one would predict that epigenetic effects might be one of these minor pathways in sexual differentiation, but more minor than most. A priori, one would predict it would be even more minor for same-sex attraction.
Epigenetics and twin studies
The arguments for a strong role for epigenetics in same-sex attraction presented in the paper, are both concerned with twin studies. Firstly, they argue that there can be many epigenetically influenced differences in identical twins e.g. they find epigenetic effects on 600 genes that can create a difference of 200% between 2 identical twins, e.g., one twin might have twice as much of a particular protein as the other. But 600 genes out of a total of about 23,000 genes is only about 2.6%, not a large effect for something they claim has a dominant role in sexual differentiation. This small fraction is consonant with other work already known (Fraga et al., 2005), unless the authors want to later make a special argument that these 600 genes are overwhelmingly critical in gender differences. So this is not a strong argument.
Secondly, they rightly point out that “estimates of proband concordance [basically the genetic influence] … are surprisingly low in both sexes” (derived from 7-8 twin studies of homosexuality ), but that estimates of unshared environmental influence are consistently high in the studies (my calculation of the average being 63% (Whitehead, 2011)). They argue that epigenetic effects belong in the unshared environment category. This category normally includes predominantly random social factors and some measurement problems but could include epigenetics. The authors, however, seem to want to say that most of the unshared environmental influences are epigenetic effects. And by this they mean pre-natal. But this is speculation and obviously awaits clearer studies.
Epigenetic changes caused by social factors
Epigenetic effects may certainly be one factor in the mix for homosexuality. But these epigenetic changes could proceed from post-natal influence (at any time in life), including social factors, e.g.,the known differing reactions of identical twins to the same environmental factors and differing reactions to family dynamics. Other experiences which differ for identical twins are probably their individual sexual experiences. The authors do not cover these possibilities, but rather make prenatal epigenetics the predominant path. Again, by analogy with other known multiple influences on homosexuality, I would vote for prenatal epigenetics being only one contributor among many.
The authors present a genetic model for the inheritance of epigenetic marks which shows that a prenatal influence could be possible and even as high as 50%. However there are several layers of assumptions and as they point out, it will be important to gather data from empirical studies, i.e., do the practical work to test their theory.
Homosexuality much more prevalent than other epigenetically caused conditions
As pointed out in My Genes Made Me Do It! Chapter 1, known congenital malformations which are epigenetic in origin occur much less frequently in the population than homosexuality. If the prevalence of these malformations is typical of epigenetic processes, this is a numerical argument that same sex attraction is not primarily caused by prenatal epigenetics.
If it is unlikely that epigenetic influences are predominant in the development of physically dimorphic gender features, i.e., male and female genitalia, then sexual orientation –a much more subtle feature of sexuality – is likely to be even less affected by epigenetics.
Useful contributions In view of the many things which could go wrong with fetal development, particularly the complexities of the testosterone pathway, it is extraordinary that the human race and mammals in general are so sharply divided into male and female, and disorders of sexual development are so relatively rare. The authors give good evidence that there are many missing pieces in our knowledge. They cite half a dozen pieces of evidence for canalization to heterosexuality but their mistake is to want to fill most of the missing pieces with epigenetics. The paper is a useful correction to many incorrect opinions held by the general public. For instance it points out that for “more than a decade… no consistent evidence for a major gene or other genetic marker” for same-sex attraction has been found. This is true. They are probably right in their emphasis that the known overlap in prenatal testosterone levels between male and female foetuses is not important for dimorphic genitalia development. But, as discussed, they are almost certainly wrong in their suggestion that epigenetics is responsible for it instead.
They also give a plausible account of how a reproductively deleterious trait like homosexuality could survive genetically.
The paper brings together a wide range of knowledge from many fields, and establishes a possible role for epigenetics. But firm results are needed from eager researchers in those fields before it can be said that epigenetics has anywhere near a predominant role in male/female differentiation, let alone sexual orientation. In my view this paper risks joining the many other efforts to show a powerful biological causality in homosexuality, all of which have failed.
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suner, D., et al. (2005). Epigenetic differences arise during the lifetime of monozygotic twins. Proceedings of the National Academy of Sciences, 102, 10604–10609.
Lombardo, M. V, Ashwin, E., Auyeung, B., Chakrabarti, B., Taylor, K., Hackett, G., Bullmore, E. T., et al. (2012). Fetal testosterone influences sexually dimorphic gray matter in the human brain. Journal of Neuroscience, 32(2), 674–680. Retrieved from 22238103.
Rice, W.R., Friberg, U. Gavrilets, S. (2012). Homosexuality as a consequence of epigenetically canalized sexual development. Quarterly Review of Biology, 87(4), 343-368.
Whitehead, N. (2011). Neither genes nor choice: Same-sex attraction is mostly a unique reaction to environmental factors. Journal of Human Sexuality, 3, 81–114.
Whitehead, N. (2014). Prenatal hormones are only a minor contributor to male brain structure in humans. Journal of Human Sexuality, 6, 104-126.