Not Even Yong

There was some noise at ASHG about someone (Tuck Ngun) claiming that he’d found evidence supporting that idea (published a couple of years ago) that homosexuality might be caused by epigenetic leakage. Which I doubted.  Everyone seems to have disbelieved Ngun’s claim, mainly because the study had no statistical power. He looked at discordant identical twins (which I think could be very informative if done right, although low N) and tried to see if some subset of the epigenetic state of thousands of loci might predict homosexuality.   Multiple hypothesis testing, uncorrected, bad.

Ngun’s work is probably worthless. It doesn’t disprove the leaky-epigenetics theory, it’s just no evidence at all.

What you want to do is look for is a difference in the brain between those discordant identical twins. Sure,  geneticists want to do genetics, but that’s not the way to go in this case. Look at neuron subpopulations, something like narcolepsy.  More likely in the hypothalamus than the frontal lobes.  While you’re at it, you’ll likely find out quite a bit about the neuroanatomical basis of male sexual behavior.

Of course, no one could get funding for this, and if someone did succeed, he would become an unemployable pariah… Not every researcher is that curiosity-driven.

Here is one scenario for the discovery of the cause that actually could happen – although there are others..  Consider the case of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a synthetic street drug that, by accident, zapped the neuron subpopulation involved in Parkinson’s disease.  Instant Parkinson’s, in young people. We learned a lot about the disease from those brave junkies.

Posit a new synthetic heroin, another China White, that by sheer accident zaps the particular neuron subpopulation that triggers/implements male sexual attraction (and nothing else) .  Suddenly, Bob’s not just your uncle any more. With that kind of clue, we’d get to the bottom of things in no time.  There would be no fundamental difficulty in determining the naturally-occurring causes of that particular neural ablation, such as infection, toxins, or in rare cases mutation (all of which we have seen with Parkinson’s disease).

Then we would understand.

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37 Responses to Not Even Yong

  1. 415 reasons says:

    The very scenario you described (drug side effect causes gay behavior) has already happened and no surprise it was a dopamine agonist drug for treating Parkinson’s. http://abcnews.go.com/Health/parkinsons-disease-patient-wins-lawsuit-gay-sex-addiction/story?id=17839255

    • Sean says:

      Dopamine receptor drugs are well known for causing odd behavior such as excessive sex drive (patient’s wife called the cops to get him to leave her alone) , gambling (lost life savings at casino in one session) and perfectionist gardening (using leaf blower machine for several hours a day).

  2. caethan says:

    According to Yong, it doesn’t count as a hypothesis test if you discard models because they’re “unsatisfactory” (on the test set). As long as you don’t calculate a p-value, no multiple hypothesis testing that needs to be corrected!

    • Alex says:

      What he means is that he split his dataset into two parts and he did the “multiple comparisons” on one subset and did his hypothesis testing on the other part.

      Whether the validation was done on the training set or the testing set seems to be the main issue.

  3. Handle says:

    There are folks doing a lot of brain scanning now for other reasons. The hot thing is testing child brain development, every few years for the study participants, to try and figure out how poverty, oppression, and hate create disparate impacts on neurology, so that one day we can close all the gaps. My own son got scanned as part of a local study for this reason.

    The grant ‘justification’ is silly, of course, however, we should encourage this kind of thing and get a ton of money thrown at it. The One Million Kid Scan project.

    Then you do a follow-up in adulthood, and bury some questions about sexual orientation in the long survey.

    Then someone can pull a Chetty and get all the data purportedly to prove some officially desirable thing like he did with taxes, but, oh no, by making the data public (or maybe it gets leaked) someone else – anonymous or with nothing to lose – throws all the images in the Big Data machine and actually generates some understanding on the question. On lots of questions.

  4. JayMan says:

    I mentioned to people shortly after seeing this study that it was dead-on-arrival.

    Added this to the “master list” on the topic:

    Greg Cochran’s “Gay Germ” Hypothesis – An Exercise in the Power of Germs

  5. Greying Wanderer says:

    “Of course, no one could get funding for this, and if someone did succeed, he would become an unemployable pariah””

    The Chinese ought to try and find out before they find out they hard way if they have less immunity than everyone else.

  6. Toddy Cat says:

    If there was a drug that turned gay people straight, I wonder what percentage of the gay community would take it? More appositely, I wonder what percentage of parents would (probably surreptitiously) give it to their kids…

    • Ziel says:

      Yes interesting question. I’d imagine that one drawback the pill’s recipients might find is that being attracted to women can be a hell of a lot more frustrating.

    • Mark F. says:

      Interesting question. I’m gay and wouldn’t take it. It would be a disruptive change in my life with no real benefits. But I suspect 90% of parents would give it to their kids, if not more.

  7. epoch2013 says:

    Is there an epidemic of homosexuality among recently discovered hunter-gatherer tribes?

    I think the question is interesting because I would suspect that the non-existence in hunter-gatherers that Greg points to in this link: https://westhunt.wordpress.com/2012/02/16/depths-of-madness/

    A pathogen would neatly explain that. But we all know that populations isolated from pathogens likely suffer far more from them once they get infected. Is that known?

  8. Fourth doorman of the apocalypse says:

    This paper from 2012 claims Out Of Africa has been disproven:

    http://file.scirp.org/Html/19566.html

  9. peppermint says:

    …but why do you even think there are “gays”? Why can’t they just be perverts with a fetish for sex play with other men in a way that has bonding and social status implications?

    Are “gays” really not interested in sex with women? Who says so? Kinsey didn’t.

    Transgenderism as a way to sneak past mate guarding behavior or into female safe spaces is known to exist in several animal species.

    • MawBTS says:

      …but why do you even think there are “gays”? Why can’t they just be perverts with a fetish for sex play with other men in a way that has bonding and social status implications?

      That seems to be what male homosexuality in other animals amounts to. Bonding. They still breed with females if they get the chance.

      Human male homosexuals…don’t. In San Francisco in the 80s the fertility of gay men was something like .2.

      Transgenderism as a way to sneak past mate guarding behavior or into female safe spaces is known to exist in several animal species.

      Again, that happens in other species, but not ours. A woman thinking you’re gay = end of any chance you might have had with her. There’s the friendzone, and then there’s the gayzone.

      • gcochran9 says:

        Martians are familiar with various biological patterns seen in other species, such as male morphs (‘sneaky fuckers’) ( perhaps they read about them in a book?), but since they have never met or had significant experience with human beings, they often go awry. They don’t know that homosexual men are sexually uninterested in women. They talk about gay men’s special avuncular investment, even though A. it would have to be impossibly large and B. it doesn’t exist. And so on.

        • Sean says:

          “They don’t know that homosexual men are sexually uninterested in women” That is true by definition, but many homosexual men are interested in young smooth skinned feminine men. I don’t think it so unlikely that many homosexuals are pseudo gay by default , maybe with a schizophrenia spectrum disorder that kept them out of the mainstream socialising.

          I think like schizophrenia and Alzheimer’s, it will turn out that there are many forms of biological insult converging on a single syndrome.

    • gcochran9 says:

      You are a Martian.

  10. erica says:

    “What you want to do is look for is a difference in the brain between those discordant identical twins. Sure, geneticists want to do genetics, but that’s not the way to go in this case. Look at neuron subpopulations, something like narcolepsy. More likely in the hypothalamus than the frontal lobes.”

    At least there is “gender” research, and it does include research on the POA. The latest find ( in rodents, of course) is that methyltransferase is more abundant in the default female brain and that in development, its presence puts a lid on the male brain until very late in gestation when a release of testosterone by the testes results in the reduction of methyltransferase, resulting in demethylation, allowing for the expression of male reproductive traits. Might problems in this area be responsible for mate targeting as well?

    One wonders if , in the case of homosexuality 1) there has been a failure to “un-cap” some of those genes to allow male expression because of some glitch in the demethylation process; 2) if there might be some foreign presence (a pathogen maybe?) that is imitating methyltransferase, keeping the lid on, so to speak, and maintaining some female traits 3) if this could explain why some gay men are more fem than others…with any glitches resulting in fuller demethylation (and thus, fuller masculinization) in some than in others?

    Much of the press, don’t ya know, (and even some of the researchers) seemed to present the results of this study as evidence of the malleability of gender. I suspect the researchers were treading lightly with their comments, mindful of the dangerous pc waters in which they are swimming, but it seems to me this kind of study will lead, eventually, to the discovery of the precise place in the brain where mate identification lies…and then? We’ll see. What unlucky group of scientists is going to have to explain to people how and when heterosexuality is established? And what mucks it up.

    Another find from the study: windows for development of the gendered brain extend beyond birth and “that microglia, or inflammatory immune cells, may be involved in masculinization because they produce prostaglandins, a neurochemical that’s typically linked to illness.” Hmmm.

    http://www.genengnews.com/gen-news-highlights/brain-gender-altered-by-lifting-epigenetic-repression/81251103/
    http://www.ncbi.nlm.nih.gov/pubmed/25821913

    • erica says:

      #3 above should read, “if this could explain why some gay men are more fem than others…with any glitches resulting in less demethylation (and thus, less masculinization) in some males than in others?”

    • Richard Sharpe says:

      One wonders if , in the case of homosexuality 1) there has been a failure to “un-cap” some of those genes to allow male expression because of some glitch in the demethylation process; 2) if there might be some foreign presence (a pathogen maybe?) that is imitating methyltransferase, keeping the lid on, so to speak, and maintaining some female traits 3) if this could explain why some gay men are more fem than others…with any glitches resulting in fuller demethylation (and thus, fuller masculinization) in some than in others?

      When would it have to occur? During meiosis? During fertilization? Before the neurons involved are laid down? After?

      • erica says:

        Well, in the rodents, the demethylation they were looking at that allowed expression of reproductive traits like anogenital sniffing and thrusting occurred very late in gestation and even AFTER birth.

        “These sex differences in the brain are programmed toward the end of fetal development, through to one week after birth in rodents.”

        http://www.the-scientist.com/?articles.view/articleNo/42555/title/Female-Brain-Maintained-by-Methylation/

        • Fourth doorman of the apocalypse says:

          That is interesting because in CAH females, masculinization seem to occur in the uterus.

          It is claimed that on average male humans have longer forearms than female humans (probably has more uses than …)

          I wonder if CAH females have longer forearms than non-CAH females, on average.

          I wonder if anyone has tested CAH females for male-typical behavior vs female-typical behavior at young ages?

        • Fourth doorman of the apocalypse says:

          That paper says:

          “Our understanding that the female state of the brain is the default still stands. What changes now, because of this study, is our thinking as to how the default state is preserved,” said Geert de Vries, director of the Neuroscience Institute at Georgia State University who studies how sex influences the developing brain but was not involved in the work. “The authors show that there is active repression of the masculine brain program, and that is really a novel idea.”

          If there is active repression of the masculine brain program, then how can the female state of the brain be the default state?

          • erica says:

            Thought the same thing when I first read of this, but then I know next to nothing of embryology. Guess it all depends on the sequence of events. First line of the abstract: “The developing mammalian brain is destined for a female phenotype unless exposed to gonadal hormones during a perinatal sensitive period.”

          • Richard Sharpe says:

            The developing mammalian brain is destined for a female phenotype unless exposed to gonadal hormones during a perinatal sensitive period.

            Do individuals with Androgen Insensitivity Syndrome evince the full female behavioral phenotype (minus the reproductive bits)?

            Of course, we would need a definition …

          • Fourth doorman of the apocalypse says:

            The developing mammalian brain is destined for a female phenotype unless exposed to gonadal hormones during a perinatal sensitive period.

            Which female phenotype is that? The Sub-Saharan African female phenotype, the East Asian female phenotype, the Caucasian female phenotype, the Pygmy female phenotype?

            I think there is plenty of evidence that those phenotypes are not all the same.

    • Richard Sharpe says:

      I do like their use of that scary word “repression.”

      • erica says:

        LOL.
        Then you’ll like the statement in the link I just gave: ” ‘In other words, male hormones unleash the male program. ‘It’s an emancipation, you might say, of these genes that are suppressed by the female. ‘ ”

        We women are such shrews. 🙂

    • melendwyr says:

      This hypothesis suggests that there should be men who, despite being heterosexual, have varying degrees of ‘female’ neurology and thus feminine behaviors and personalities. You might be able to look for similar sorts of brain development patterns, and since sexuality wouldn’t be an issue, it might be easier to perform studies.

      Human women are more like men, sexually, than most mammals are. I’ve sometimes wondered if male homosexuality is part of the ‘price’ we pay for men becoming more like women than most male mammals are, and the hit-or-miss process screwing up occasionally.

  11. Matt says:

    Seems like people might be able to do one of those identical twin neuron studies in paedophile vs non-paedophile discordant twins, then that might be able to generalize back.

  12. Sinij says:

    “and if someone did succeed, he would become an unemployable pariah… ”

    I think being on the cover of Times magazine will more than make up for some attempted ostracizing.

  13. Casey says:

    What about this new study:

    http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134817

    Could you do a write-up on it?

  14. JayMan says:

    Maybe someone had your theory in mind for this one:

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