Since the mid-1990s I’ve been thinking about a pattern that seems significant. There are a whole range of what you could collectively call “brain organization traits” that are commoner in males than females. Left handedness, lower or later verbal development sometimes paired with higher math ability, slower social development through the whole spectrum to Asperger’s and autism, homosexuality, and no doubt I’m missing a few. The difference isn’t always large, for instance left handedness shows only a 1.23:1 male:female preponderance, but it is statistically significant. Asperger’s, on the other hand, is diagnosed at about 4:1 males:females. Homosexuality approximately 3:2, dyslexia, about 3:1.

That is odd. The ratios are unlike, say, color-blindness which is an X-linked trait and hence necessarily more prevalent in males. (Just some bio background for those who might want it: men have one X, women have two. Therefore women have two copies of any X-linked gene and a much higher chance that any given genetic information on one X can be masked by the other copy. That’s why X-linked conditions mostly show up in men.)

So it has to be some unstraightforward factor that affects males more than females. No post-natal environmental factor has ever been reliably identified for any of those traits. The traits all have to do with neurological pathways. It seemed logical that the prenatal environment which affects brain development was the place to look. Sex hormones like estradiol and testosterone play critical roles in brain development. And there’s one very obvious prenatal difference between males and females: all mothers are female, so female fetuses are likelier to have a hormonal environment aligned with their own than male ones.

In 2006 I wrote about this, including links to some of the research surfacing at the time. More and more evidence is accumulating showing the effect of fetal hormonal influences.

Elevated Fetal Steroidogenic Activity in Autism. 2014. Popular version:
Children with autism have elevated levels of steroid hormones in the womb From the popular article: “children who later develop autism are exposed to elevated levels of steroid hormones (for example testosterone, progesterone and cortisol) in the womb.” Also, from a BBC article: “Prof Baron-Cohen [one of the study authors] said: “This is one of the earliest non-genetic biomarkers that has been identified in children who go on to develop autism. We previously knew that elevated prenatal testosterone is associated with slower social and language development, better attention to detail, and more autistic traits. Now, for the first time, we have also shown that these steroid hormones are elevated in children clinically diagnosed with autism.”

Remember that there could be any number of sources for unusual hormones. The placenta-uterine interface could be unusually permeable, allowing more of the mother’s hormones through. The fetus could over- or under-produce hormones. Hormones from a non-identical twin can have an influence. Also, this is biology. Everything could work together in varying degrees. As they say, it’s complicated.

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder. 2014. Popular article: Study shows environmental influences may cause autism in some cases (“Environmental” in this case refers to the uterine environment of the fetus.) “The researchers detected two groups of genes that were epigenetically distinctive in children with ASD compared with TD [Typical Development] children. Moreover, these genes are known to be expressed in the brain and code for proteins involved in nerve transmission functions previously shown to be impaired in ASD. Interestingly, these two groups of epigenetically distinctive genes weren’t present in all the cells of children with ASD but only in a subset of them—a phenomenon called mosaicism.”

Mustanski et al. 2005. Human Genetics (pdf) This paper discusses the nonrandom inactivation of a given X chromosome. That’s unusual, the mechanism isn’t known, and it would affect males, with their single X, more than females.

Minireview: Hormones and Human Sexual Orientation. J. Balthazart. 2011. (Supposed to be available from NCBI, but link not currently working for me.)

It is not all hormones: Alternative explanations for sexual differentiation of the brain. Davies and Wilkinson. 2006. From the abstract: “[W]hile gonadal hormones undoubtedly play an important role in sexual differentiation of the brain, they are not the only possible mechanism for this phenomenon. In the present review, we discuss the concept that genes residing upon the sex chromosomes (which are asymmetrically inherited between males and females) may influence sexually dimorphic neurobiology directly….”

Molecular studies of dyslexia : regulation and function of DYX1C1. Tammimies. 2011. The gene in question regulates fetal neuronal migration and is influenced by estradiol.

And I could continue on like that through hundreds of references.

One implication, if these traits can have common roots in hormone levels during critical periods of fetal development, is that similar mutations could result in seemingly unrelated traits. A lineage being studied for, say, the heritability of mathematical ability, should also be polled for other brain organization traits. Genetic studies might then more readily pinpoint common mutations which are likelier to underlie the neurological processes.

Switching gears now to talk about social rather than biological implications, fear often seems to surface when there’s any talk of departing from a “genetic” cause of homosexuality to factors that could be manipulated.

I think that fear is misplaced on several counts. One is that purely as a practical matter, genes are not immutable. Their expression, which is what we care about, is hugely influenced by the environment. Furthermore, it’s only a matter of time before all genes can be directly manipulated. Basing acceptance of a trait on its genetics is very shaky ground to stand on.

The bigger problem, though, is what the nothing-but-genetics attitude implies. The idea is that it forces people to accept homosexuality because it’s a not-my-fault-I-found-it-that-way situation.

That’s silly. It accepts the frame that difference from the majority is a “fault” that should be erased if one could. Instead the point is that difference is okay. Whether it’s genetic or congenital or learned or chosen does not matter. We need all the Einsteins and Marie Curies and Oscar Wildes we can get.

Last, and most important, as a matter of principle, rights have nothing to do with genetics. Everybody has the right to make their own choices, so long as they don’t actively harm others. As I said in the earlier post, “the most important point is that genetics says nothing about how people should live their lives. The most important point is that sexuality is nobody’s business but your own. It doesn’t matter whether it’s a choice or not. The whole debate is useless, because the whole debate is nobody’s business.”