GWAS and the Fatal Conceit: Or Why Your Gay Gene Is No Longer Happy

[roo_ster]

....or your happy gene is no longer gay....or your aggressive gene is taking a powder...


The upshot is that using genome-wide association studies (GWAS) to find a genetic cause for mental processes that are effected by multiple genes is no more valid than your typical fuzzy-science sociological study.

So, folks who make noise about "aggressiveness genes," "happiness genes," "gay genes," and the like are on much less solid ground that they would have you think. 

To put it another way, GWAS is about as valid violent video games / violent crime studies for complex mental phenomena.



All bold-face is mine.


http://corner.nationalreview.com/post/?q=ODQxZDNhYTQ4NGRkYzRhMWRlMDQ3ZTI1YjIyMTcwZjU=

Goldstein, Genes, and the Fatal Conceit   [Jim Manzi]

Andrew Sullivan points to some the blogosphere discussion arising from Dana Goldsteins emperors-new-clothes article about the failure of genome-wide association studies to find genes that account for human mental states (as well as other non-mental conditions).

Goldstein is putting forward a theory for why it is plausible that evolution would have created such a situation. But whether or not Goldstein is correct about the causal pathway that created this situation, it is an empirical reality that a GWAS has a very hard time finding genes that create given mental states. This is fundamentally a problem of combinatorial mathematics.

Heres how I put it in a National Review article in June:

    Media outlets will often speak loosely of things such as a happiness gene, a gay gene, or a smart gene. The state-of-the-art method for finding such a link is something called a genome-wide association study (GWAS). In a GWAS, scientists use blood or saliva samples to sequence the DNA for a group of several thousand people who exhibit a trait or behavior of interest (the case group), and for a second group of several thousand who do not exhibit the trait or behavior (the control group). Scientists then look for genetic differences between the two groups. In cases where a single malfunctioning gene creates, for example, a catastrophic disease that overwhelms other genetic and environmental factors, a GWAS can quickly pinpoint the culprit. Sometimes, however, the behavior or trait is caused by several interacting genes  so that, for example, Gene 1 has some effect only if Gene 2 has a special structure. This is called epistatic interaction, and can involve a large number of genes. Epistatic interactions make genetic effects harder to identify. Scientists deal with this problem and others by creating larger and larger case and control groups. The scaling up of such studies is among the most exciting frontiers in genetics. It is essentially an engineering problem, and money poured into solving it will likely improve human health through genetic screening and, ultimately, therapies.

    Seeing this momentum, it is natural to assume that eventually we will have explained all human behavior, not just diseases caused by one or a small number of interacting genes. But the GWAS technique hits structural limits when applied to conditions that involve epistatic interactions among lots of genes. Mental activity is now widely believed by scientists to depend on many genes (though mental illnesses such as schizophrenia or bipolar disorder may turn out to be partial exceptions). A person has about 20,000 genes, of which more than 5,000 are believed to play some role in regulating brain function. Consider a simplified case in which some personality characteristic  aggressiveness, for example  is regulated by 100 genes, each of which can have two possible states (on or off). The combinatorial math is daunting: There are more than a trillion trillion possible combinations of these gene states. Thus we could sequence the DNA of all 6.7 billion human beings and still not know which genes are responsible for aggressiveness.

    A second limitation of a GWAS is that it detects association rather than causation. Suppose we found that a case group of persons suffering from a disease had a greater incidence of some gene than did a control group, but that we failed to notice that the case group was disproportionately of Chinese ancestry. Culturally transmitted behaviors in the case group might be responsible for the disease, even if these behaviors had nothing to do with the gene in question. That is, the gene could be nothing more than a marker for Chinese ancestry, and hence for participation in behaviors that cause the disease. Geneticists call this problem stratification, and deal with it by carefully matching individuals in the case and control groups to ensure that the groups really are comparable. The problem is that these stratification effects can be fiendishly subtle. No matter how carefully we match cases with controls, there can always be some unobserved environmental factor correlated with, but not caused by, a genetic difference between groups, and this environmental factor might be what is actually causing the disease.

    Further, to think in terms of genes is to abstract away from a biochemical reality that is far more complex. On one hand, a gene is not an atomic entity, but a sophisticated machine with many components. Much as in the progress of particle physics over the past century, we keep discovering components-within-components of the genetic mechanism that are relevant to physical and mental outcomes, and its entirely plausible that we will eventually get all the way down to subatomic quantum effects as drivers of behavior. On the other hand, as we move away from the genome itself, we see that other dimly understood biochemical processes have a large impact on how the information contained in the gene gets expressed as an observable human characteristic. And all of this is before we consider interactions of the human organism as a whole with those factors that we typically term environmental, ranging from nutrition and exposure to pathogens to parenting styles and childhood experiences.

    So how is a GWAS showing an association between Gene X and aggressiveness different from a social-science study showing a correlation between watching lots of violent TV and aggressiveness? Mathematically, its not. In both cases we start by measuring aggressiveness for each person. We then compile for each person a list of data providing information on potential causes of aggressiveness: in one case genomic information, and in the other, sociological observations on childhood experiences, school quality, and so on. In the first case we observe that aggressive people have a higher incidence of Gene X; in the second that they watch a lot of violent TV. The reliability of GWAS studies is thus subject to the same limitations that we think of in connection with sociology or economics (as opposed to, say, chemistry). The only way around this  the only way to attain the precision of chemistry  would be actually to show the chain of biochemical processes by which a set of named genes creates the observable brain functions collectively defined as aggressiveness. Of course, if we could do that, we would have no need for a GWAS study.

    The claims of causality that arise from such studies should accordingly be treated with the appropriately intense skepticism that we apply to sociological or econometric studies. In the middle of the 20th century, Friedrich Hayek and the libertarians he inspired faced those who asserted that that an economy could be successfully planned. The libertarian position was not that such planning could be proved impossible in theory, but that we lacked sufficient information and processing power to accomplish it. The world of economic interaction is so complex that it overwhelms our ability to render it predictable; hence the need for markets to set prices. This is the same analytical problem we face when trying to predict a mental state that depends upon a large number of genes. It is unclear whether we will ever understand how this complicated machinery and its interactions with the environment come together to create characteristics of mind. It is certain, however, that we do not have such an understanding now, and that we wont know such a project is achievable until we achieve it.


Perhaps we need a LHC for the genome.  We accelerate two folks at near light speed and have them collide.  After the cleaning crew hoses down the mess, maybe we will have learned something...

[roo_ster]

Oh, this is not a "homosexuality is wonderful/terrible" type of post. 

It is a heads-up on the reliability of claims made in the bilogical sciences.

Gay/happy is a play on words.

[Dntsycnt]

People often approach science as magic or scientists as prophets...it would be greatly beneficial to smash that perspective, especially in the mainstream media.

Always good to see a little light shown on such things.

[Perd Hapley]

My gay gene is feeling just FAAAAAAAAABULOUS, thank you.  But my blame-everything-on-genetics gene is very upset and confused. 

[ilbob]

People often approach science as magic or scientists as prophets...it would be greatly beneficial to smash that perspective, especially in the mainstream media.

Always good to see a little light shown on such things.

when it turns out there is no gay gene, and its just a learned behavior (as it probably truly is), does that have any ramifications?

[taurusowner]

Well it would call a lot of discrimination and hate crime law into question, since those are supposed to be based on things you cannot change, like race or being stuck in a wheelchair, etc.  If homosexuality turns out to be a learned behavior, meaning, a choice; then laws about discrimination based on homosexuality would have grounds for questioning.

[BrokenPaw]

I note that the gist of this article is "we have not found a causal relationship between genes and some attributes that people have asserted are genetic, and probably never will".  It is not saying that such things are conclusively not caused by genetics.

And yet, already in this thread, there is the non sequitur "see, I knew that homosexuality was a learned trait."

All the article is saying is that there's no simple way to prove genetic causality via GWAS.  The fact that GWAS cannot prove causality is not, in and of itself, proof that such a causality does not exist. 

The fact that we cannot prove something exists is not prima facie evidence that it does not or cannot exist: There is no conclusive evidence of the existence of the God of Abraham; does that prove that He does not and cannot exist?  No.

I am not asserting that such causality necessarily does exist; but one post on this thread has already opined that because GWAS can't prove it, it isn't there: 

when it turns out there is no gay gene, and its just a learned behavior (as it probably truly is)

Specious argument.  Rejected as not germane to the subject.

-BP 

 

[Perd Hapley]

Why the getting all bent out of shape about the nature vs. nurture question, RE homosexuality? 

[ArfinGreebly]

Well, let me speculate.  I will suggest not reading too much into what follows, as it has some controversial "edge" conditions.

If I can go to jail because someone can assert that something I said constitutes "hate" speech against a group whose claim to protected status has no provable foundation . . . that's kind of a big deal.

If a lawmaker can criminalize actions "against" some group whose assumed genesis is a matter of nature, when this factually cannot be proven, and if I happen to disagree with a precept (or all the precepts) of said protected group, and if my disagreement is determined to be afoul of this law, then what we're doing is policing thought.

If I say something like, "it is wrong to be black, and is contrary to nature," then I'm pretty much a bigot and an idiot in the bargain.

If, on the other hand, I say something like, "it is wrong to be gay, and is contrary to nature," and if it turns out that "gay" is a LEARNED behavior -- a fetish, as it were -- then am I still a bigot?

Teaching children to discriminate based on skin color is a detestable thing.

So, what about teaching children to condone a sexual fetish, something about which they will later be educated and into which they will, with luck, be indoctrinated and inducted, would this not also be a detestable and contemptible thing?  That's straight up child abuse.  Grooming behavior.

Now, if it turns out that "gay" is a genetic thing, and that learned behavior is really not a factor, then the ridicule of a person whose sexual inclinations are, essentially, pre-programmed, well then, THAT would be detestable.

So it's kind of important whether it's "nature or nurture" when it comes to sexual "wisdom" being taught at an early age.

If it's nature, then it is well to be informed and essential to be understanding.

If it's nurture, then, frankly, it's seriously abusive to "teach" it to children.

The implications of "well, yeah, it's a choice, but it should still be tolerated and endorsed" extend well beyond what is, on its face, a relatively harmless sexual fetish.  If a fetish is a choice, and any choice is as valid as any other choice, and we want to indulge in some industrial-strength moral relativism, then torturing pets is just another "lifestyle" choice.  And it's not far from there to "anything goes."

As long as it's a matter of LAW that "gay" is a naturally occurring condition, then it also follows logically that bigotry and discrimination against it are proscribed.

What happens when it turns out that this assumption is found to be broken?

What follows logically from that?

Do we adopt the position that, well, it's essentially harmless, so what's the big deal, just leave the laws in place?  Where does that take us?

Maybe we should just abandon the idea of "child abuse" entirely and educate children to expect anything and everything.  Hey, kids, just give everything a try.  Maybe you'll find something you'll like!

Does any of this make sense?

Because, if "gay" is a naturally occurring condition, what about pedophiles?  Naturally occurring condition?  How can you punish something that's burned into the factory ROM?  What's Darwin have to say on this?

It would seem to me that our system of "right" and "wrong" and what's permissible and what's not needs to have place for its foundation that's not continually affected by some kind of moral subsidence.

Please feel free to point out the holes in my reasoning.  I won't claim to have gotten it right, but I think there's more than a shrug involved.

[Dntsycnt]

Really?  Comparing homosexuals to pedophiles again?  I thought we were past this long ago.

How about we discuss the actual issue at hand, instead of extraneous BS that has been argued to death and no one will change their positions on?

[Perd Hapley]

I think it is about time that both sides understood something; being born a certain way doesn't make it OK.  To the pro-homos, that argument is a non-starter.  To my fellow "haters," we don't have to win that argument.

[taurusowner]

We'll never be past it, especially since there are indeed pedophilia advocacy groups, loony to be sure, that are claiming they should receive the same acceptance and protection as homosexuals for the same reasons.  Don't forget that a few decades ago, homosexuals were seen with the same criticism as pedophiles.  Now they're not.  It doesn't take a  genius to see that the same path homosexual advocates took to gain acceptance, is the path others who promote (what is currently) deviant activity are taking to the same end.  "It worked for the gays, it can work for us".  And they may be right.  It's not like pedophilia has always been condemned by every society.  Many other civilizations in the past, and some present, accept and even promote/d pedophilia.  It isn't that far of a stretch to think it may happen here if the social climate and attitude changes to become favorable and understanding to it.

[BridgeRunner]

Because, if "gay" is a naturally occurring condition, what about pedophiles?  Naturally occurring condition?  How can you punish something that's burned into the factory ROM?  What's Darwin have to say on this?

It would seem to me that our system of "right" and "wrong" and what's permissible and what's not needs to have place for its foundation that's not continually affected by some kind of moral subsidence.

Why?  It seems like in your preceding paragraph you just explained why "natural" is not a good way to evaluate acceptable behavior.  

On a cultural level, each community determines what is acceptable behavior.  I spent time in a community where gay inclinations are not openly discussed.  I spent time in a community where gay activity was strongly encourage.  I live in a commuity where gay inclinations are widely acknowledged, but gay behaviors are proscribed.   Diversity is nifty that way.  

On a legal level, we have moved to a large degree to a system that determines what is acceptable based on personal autonomy and the general right to engage in consensual sexual activity, with the caveat that children cannot give consent.  

All kinds of ways of perceiving and dealing with gayness in its various manifestations.  Genetics does not really play into any of them.

It's when one fall into thinking of complex issues in terms of over-simplistic absolutes, like "genetic->natural->ok" that problems arise.  We have thousands of years of cultural and religious and social and moral and ethical traditions that help us determine how we respond to homosexuality in its various manifestations.  Why on earth should we try to redefine such an important issue down to genetics?

So, yeah, this is kind of insignificant to me.  There is so much more than just genetic/not-genetic that plays into this.

[grampster]

I heard they just stumbled upon "the more things change the more they stay the same" gene.

[taurusowner]

On a cultural level, each community determines what is acceptable behavior.  I spent time in a community where gay inclinations are not openly discussed.  I spent time in a community where gay activity was strongly encourage.  I live in a commuity where gay inclinations are widely acknowledged, but gay behaviors are proscribed.   Diversity is nifty that way. 

Except for the outcry from many leftists that parents should not be allowed to teach their own children anything other than homosexuality is OK and normal.  And any parent who believes and teaches otherwise should be held legally accountable.  It's not enough for them that they can think it's fine, and I can think it's not, and we both teach our kids what we feel is best. 

[Antibubba]

taurusowner said:

Well it would call a lot of discrimination and hate crime law into question, since those are supposed to be based on things you cannot change, like race or being stuck in a wheelchair, etc.  If homosexuality turns out to be a learned behavior, meaning, a choice; then laws about discrimination based on homosexuality would have grounds for questioning.

What they're saying is that the presence (or absence) of any single gene isn't likely to cause a specific behavior.  So while there's unlikely to be a "gay" gene, there might be several genes across several chromosomes that, when activated somehow, might influence a person's sexual preference.  Keep in mind that behaviors can be stimulated by other internal factors, such as hormones.

And while the the presence of certain genes that have been found in certain demographics might mean that that person might exhibit those certain behaviors, it is a leap to say that those genes cause that characteristic.  In testing done among manic depressives, for example, certain genes show up fairly regularly, but they can also show up in family members who have never exhibited those behaviors.

But, although it is not trackable to a specific gene or set of genes, I'm very skeptical of those who insist that homosexuality is simply a learned behavior or "choice"; given the gays I've met whose native cultural taboos make Pentacostalism look like Mardi Gras, I can't believe that external factors are the only cause.

[Perd Hapley]

I'm very skeptical of those who insist that homosexuality is simply a learned behavior or "choice"; given the gays I've met whose native cultural taboos make Pentacostalism look like Mardi Gras, I can't believe that external factors are the only cause.

And we should all be very skeptical of your underlying assumption: that breaking societal taboos can only be explained by some genetic predisposition. 

[Antibubba]

Your're assuming my assumption, Fistful. 

I have a foot in both camps--I believe sexual attraction is too complicated and rich too be attributed to "only" genetics or "only" environment.

[86thecat]

If SWAG is a Scientific Wild ass Guess would this study (GWAS) be Guess, Wild ass Scientific?   

[ArfinGreebly]

I believe sexual attraction is too complicated and rich too be attributed to "only" genetics or "only" environment.

I think it's plain enough from simple observation that reproduction through sexual congress is about as basic as it gets in the perpetuation of the species department.

I would say it's a safe bet that an overwhelming majority of land-based species -- specifically vertebrates -- have that hard wired in.

Given that this is, from a survival of species perspective, both natural and desirable, any deviation from that wiring is pretty clearly a departure from norms and a deviation from desirable function.

That would be an aberration.

It's conceivable that there's a genetically broken pattern that departs from that norm.

However.

The idea that its a good plan to build a social and cultural construct around that malfunction . . . that's a real stretch.  I mean, really.

And that's going with the assumption that it's somehow organic.

Things don't get better when the assumption is changed to one of choice.  Or even one of "choice" as a manifestation of Stockholm Syndrome.

One thing's for sure, though.  The guys making the laws don't have a friggin' clue.

[MicroBalrog]

If, on the other hand, I say something like, "it is wrong to be gay, and is contrary to nature," and if it turns out that "gay" is a LEARNED behavior -- a fetish, as it were -- then am I still a bigot?

Let's see. A person's religion is also not genetic. People, at least to some degree, choose their faith.

So, are you a bigot if you say "It is wrong to be Christian, and is contrary to nature"?

Given that this is, from a survival of species perspective, both natural and desirable, any deviation from that wiring is pretty clearly a departure from norms and a deviation from desirable function.

It is not my duty in any way, shape or form, to have children or continue the survival of human species.

[ArfinGreebly]

Let's see. A person's religion is also not genetic. People, at least to some degree, choose their faith.

So, are you a bigot if you say "It is wrong to be Christian, and is contrary to nature"?

Interesting point.

If there is no god, no soul, no spirit, nothing beyond the purely physical, then Man's evident predisposition to religion would more or less have to be genetic, no?

But then, in the absence of any kind of "celestial" moral authority, bigotry becomes a false concept, as it implies that there is some kind of "wrongness" with the thinking that leads to the attitudes.  If we are the product of our genes, then declaring something as "wrong" or "offensive" is nothing more than an attempt to control by nullification, an effort to ensure one's own survival at the expense of someone else's.  At which point, right and wrong become nothing more than subjective constructs.

It seems to me that "bigotry" implies moral authority which, frankly, genes do not have.

Accepting that bigotry exists, implies accepting that a moral authority exists.  Accepting the existence of a moral authority carries with it the acceptance that there is more to Man than a purely physical manifestation.

Knocking over a few more dominoes, we come to "what is the moral purpose of sex?"

That question doesn't have any meaning unless morality does, and that doesn't have any meaning unles there's more than "Man = dust" at work.

And we're back to "what purpose is served by trying to lay off a personal choice on an arrangement of genes?"

Well, that would be seeking to avoid responsibility for a moral choice, would it not?

It's an interesting concept, to assert that there's such a thing as morality, but that certain imperatives can be excused by errors on the part of the moral authority source.  Kind of a "yes, we have morality, so we'll allow that God can exist, but he makes mistakes and we get these mucked up genes, so we're not responsible for not following moral mandates."

Or, alternatively, there is no god, and nothing we do is our fault, since it's all in the genetic programming, which is entirely an accident of nature.  So, really, there is no such thing as morality, but my survival depends on controlling you, so I'm imposing the concept on you to ensure that you limit your own choices.

So, back to your question.

So, are you a bigot if you say "It is wrong to be Christian, and is contrary to nature"?

If there's no moral authority, then of course not.

If there IS a moral authority, then "nature" derives from the same source.  So, such a declaration *might* be bigotry.  Or it might simply be meaningless.

Depending on who or what the "moral authority" is.

In general, though, it's morally wrong to use morality to control others in ways that compromise their survival.

Excuse me while I try to extract my tongue from my cheek.

[MicroBalrog]

If there's no moral authority, then of course not.

I don't see why you need to believe in God to believe in the existence of moral absolutes.

I believe in the existence of moral absolutes, but I'm not so sure about God.

Outside Abrahamic religion, why is homosexuality a moral choice in the first place?

The choice of the sauce on my steak isn't a moral choice, and neither is the color of my car, or the shape of my desk. Yes, there are religions that insist that the type of food I eat is a moral choice, but as far as I know, nobody insists that it's immoral to eat pork even if you're a non-Jew or non-Muslim. There are religions that prohibit certain sexual positions.

I can deny the idea that the choice of my sexual position or my food is in the realm of morality at all without denying the existence of morality.

[ArfinGreebly]

I don't see why you need to believe in God to believe in the existence of moral absolutes.

I believe in the existence of moral absolutes, but I'm not so sure about God.

Outside Abrahamic religion, why is homosexuality a moral choice in the first place?

The choice of the sauce on my steak isn't a moral choice, and neither is the color of my car, or the shape of my desk. Yes, there are religions that insist that the type of food I eat is a moral choice, but as far as I know, nobody insists that it's immoral to eat pork even if you're a non-Jew or non-Muslim. There are religions that prohibit certain sexual positions.

I can deny the idea that the choice of my sexual position or my food is in the realm of morality at all without denying the existence of morality.

You'll note that I was careful to avoid "God" as the source of moral authority.

The point was really this:  it's an incredible leap of faith from "everything we are is represented in our genes" to the idea of morality, at all.  Never mind whether a decision to act against the naturally evolved sexual function of humanity is a moral choice, the question is, who is doing the choosing?

A bunch of highly-evolved brain cells, whose function is simply a matter of clever programming by no one in particular?

In order to "choose" anything, at all, and have it be more than the subtle interaction of nuanced synapses governed by obscure genes, somebody, a being of some sort that's NOT a product of magical evolution, has to be involved.

Where does one get this "being?"  If thought is nothing more than a bio-computer (with no designer or programmer) engaged in "a nice game of chess," with players=0, then relativism rules.  Because any entity's thinking is simply a by-product of magically accidental chemistry with a few millivolts thrown in for good measure.

If thought is, in fact, senior to function, and responsible for it, then really, it can't be the product of said function.

And that implies that there is someone home.  Someone beyond and above the mere chemistry and bio-computing.  And it is that someone who is the moral authority.

There is much that can be extrapolated from the "someone home" conclusion, but let's just see if we can establish that single basic concept.

Once it's established that there's "someone home" beyond the mere bio-function of the body, there is the issue of persistence to be dealt with.  And the issue of origins, i.e. whence comes such an entity?

In the absence of such an entity (someone home), then it's back to purely stimulus/response tricks from the accident of evolution.

Kinda hard to have a moral absolute within the framework of a highly-evolved electrified chemical accident.

It is my conviction that there is more, that there is, in fact, someone home.  That there is a non-physical component to the human condition.

Or, maybe, there is a morality gene.  Kind of a cruel joke by a creator who doesn't exist.

[Antibubba]

I think it's plain enough from simple observation that reproduction through sexual congress is about as basic as it gets in the perpetuation of the species department.

I would say it's a safe bet that an overwhelming majority of land-based species -- specifically vertebrates -- have that hard wired in.

That overwhelming majority also has a mating season--a specific time of year for starting--and stopping-- the reproductive act.  Humans are more or less ALWAYS ON, after puberty starts.  We're even interested in sex at times and ages when reproduction isn't possible.  So comparisons to the rest of the animal kingdom aren't terribly useful.