For years I’ve been carrying around an idea about how homosexuality could be inherited. The news reports that jogged me to post are the ones about the work of Mustanski et al. (Human Genetics, online, Jan 12, 2005). The research is currently being widely reported under titles like: Moms’ Genetics Might Help Produce Gay Sons (By Randy Dotinga, Feb 21, 2006) [link no longer active, article removed] [apparent repost without attribution here.]

First a few carps about the reported research, and then some thoughts on my wild(?) ideas.

The Article on genetics and gay sons

Very briefly, this is the gist of Mustanski et al., A genome-wide scan of male sexual orientation (pdf, Jan 2005, Human Genetics). Quoted from the yahoo news article mentioned above:

Women typically inactivate one of their two X chromosomes at random. “It’s like flipping a coin,” Bocklandt [one of the authors] said. “If you look at a woman in any given (bodily) tissue, you’d expect about half of the cells to inactivate one X, and half would inactivate the other.”
…
“When we looked at women who have gay kids, in those with more than one gay son, we saw a quarter of them inactivate the same X in virtually every cell we checked,” Bocklandt said. “That’s extremely unusual.”

To begin with, what about gay daughters? That wasn’t even part of the study. I’m rather boggled that the researchers expect to say anything meaningful about homosexuality when they ignore one very obvious source of perspective on their findings . (I.e. is the mother’s X-chromosome deactivation as skewed or not when she has gay daughters? In either case, what does that plausibly say about the etiology involved?)

To go on with, how do “gay kids” transform into “gay sons”? The prejudices are showing, and given that the researchers are studying something as ringed with prejudice as homosexuality, that is not reassuring. Also, although the original article shows that the researchers know they are dealing with a possible correlation and not a cause of homosexuality, that’s not stressed enough for the popular press. Note the headline that says Moms’ genetics…”produce” gay sons.

The findings are interesting, but until they reflect a much larger sample size, and more thorough attempt to see what is cause and what is correlation, this is mainly a good start for further research.

The Idea

I was intrigued by the title because I’ve thought for ages that there is an overlooked factor in a constellation of traits which depend on alterations in brain wiring and which are are more common in males than females.

The traits involved are left-handedness (slight excess: about 4:3 male to female), mathematical ability of the kind demonstrated right from the earliest days of childhood, often with associated reduction in verbal ability (I don’t have the statistics handy, but my sense is that this is more common in boys), homosexuality (about 3:2 male to female), and dyslexia (approx 3:1). There are other traits, I’m sure, but those are examples of what I’m talking about.

Hormones play an important role in establishing the “circuitry” of the developing brain, and sex hormones are among the big players. One fact of pregnancy is that the person carrying the fetus is always female. If the fetus is female, her own hormones and those of her mother are more or less in synch, and the brain wiring process is less likely to receive conflicting information even if there is a surge of “strange” hormones. It’s the other way around if the fetus is male.

The placenta is a very effective barrier and generally prevents the passage of huge molecules like maternal sex hormones. However, not all women and fetuses have equally functioning placentas. A “leakier” placenta-uterine interface might, sometimes, let through more of the mother’s sex hormones than usual. With a female fetus, this is less likely to matter. With a male fetus, especially if it comes at a critical time for brain wiring, the surge of female hormones may well alter the process.

It’s important in this context that the placenta is fetal tissue in very close association with specialized maternal tissue on the uterine side. So the genetics of either the fetus or the mother or both could play a role. Clearly, that makes things even more complicated.

The characteristics of the placenta-uterine interface depend on many factors, including nutrition, stress, and so on, but they also depend on genetics. So it may not be homosexuality or mathematical ability, per se, that is heritable. What is heritable may be a placenta or uterus that allows some maternal sex hormones to reach the developing embryo or fetus. This would make the traits in question not inherited, strictly speaking, but congenital. The placental or uterine characteristics are the inherited component.

This does not necessarily mean that, for instance, left-handed people would also tend to be dyslexic. Which trait is manifested depends on individual susceptibility, timing of maternal hormone surges, and exactly which part of the fetal brain is developing right then.

It does mean that any of these charactersitics should cluster in families. In other words, a family with lefties, should also have a higher probability of children with dyslexia, early math ability associated with late verbal ability, and so on. Depending on how big a factor the uterine component is, there might or might not be an association with matrilineal inheritance.

There are several ways to test this idea. Surrogacy, where the egg donor is not the woman carrying the pregnancy, could help to show the relative contribution of each side of the uterus-placenta equation. Genome mapping could identify areas on chromosomes that are associated with more-permeable placenta-uterine interfaces. Then the correlation between those areas and any of the traits in question could be studied. Most directly, if maternal sex hormones could be tagged in some way (not using radioactive elements, obviously) and their possible passage to the fetus tracked, and then if the children could be followed through to adulthood, that would be the most direct way to observe how close the correlation is between stages of brain development, hormonal surges, and subsequent development. The latter research project would be both complex and expensive.

The Big Issues

Whenever the discussion turns to the genetics of homosexuality, a blizzard of issues falls. People imagine future headlines like: “Christian Right Now Favors Abortions . . . In Some Cases.” Ministers who run self-help groups to “cure” homosexuality start to fear a loss of business. Legions of heterosexuals despair when they realize there is no hope for them.

Okay. I’ll admit it. I’m making fun of the whole thing because that, to me, is how ridiculous all the fears are.

Does a genetic component to homosexuality determine whether it’s a choice or a fate? No, not really, because a behavior as complex as sexual orientation is likely to be based on a whole range of causes. In some people it may be a matter of choice, in others it may be cast-iron genetics, and in others it may be anything in between. The genetic or congenital component, as with many complex traits such as intelligence or height, is more of a predisposition than an absolute law.

However, 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.

Technorati tags: homosexuality, genetics, Human Genetics, Mustanski, Bocklandt, placenta, uterus