Polymorphisms and Load

We have found that important traits such as height or IQ  are highly heritable, but that no single allele explains much of the variance in those cases. Taken as a whole,  common variants  do explain a lot,  but even they only explain about half of the genetic variance.  One question is why they should explain any of it at all.  I mean, higher IQ is good, so why should  variants that reduce it ever be common? Inspired by a suggestion by Alan Rogers, I suspect that this kind of variation involves alternate alleles that confer almost exactly the same fitness (are effectively neutral, then) yet have different effects on various components of fitness.  Tradeoff alleles. For example, an allele that drops IQ but boosts immune defense could easily be neutral.   Obviously this balance is true for some particular environment, not all environments.

Load is different: the mutations that make up load are just bad.  Such mutations almost never become common, unless the disadvantage they confer is very small, on the order of of 1/Ne or smaller ( Ne = the effective population size). And if their negative effect is  that small, they don’t matter very much.

For a given trait, some of the genetic variation is explained by the polymorphisms, while the rest is mostly explained by genetic load.  I think.

Anyhow, we now have some estimates of the relative influence of common variants on various traits (from recent Visscher-type papers) . The fraction of genetic variation that can be explained by common variants is about half for height and IQ, one-third for schizophrenia, one-quarter for  BMI, and about one-fifth for personality, as measured by standard personality measures, which I don’t have much faith in.   If I had to guess, and at this point I do, the more that trait variation is a deviation from the selective optimum, rather than being orthogonal to fitness, the more it is influenced by load.

 

 

 

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31 Responses to Polymorphisms and Load

  1. Reader says:

    http://www.businessinsider.com/genes-peter-visscher-human-intelligence-2011-8

    Business Insider billed the common variation intelligence study as “Research Finds That Genes May Account For Only 50% Of Human Intelligence,” with caveat at the end:

    “The 50 percent figure, however, is “likely to be an underestimate because we could only detect variation that is correlated with common DNA markers,” researcher Peter Visscher told HealthDay.”

  2. Zundblack Gesdorkin says:

    “We have found that important traits such as height or IQ are highly heritable, but that no single allele explains much of the variance in those cases.”

    Keep ignoring epigenetics. You’ll go far.

    • gcochran says:

      If you know of evidence of Lamarckian inheritance of intelligence, you should stop keeping it secret. And if you don’t, which is likely, since it doesn’t exist, you should find something better to do with your free time.

      • genetiker says:

        Epigenetics doesn’t imply Lamarckian inheritance. It’s really just an expansion of our concept of genetics. It’s a second genetic layer, one which functions somewhat differently than the first one. While the first one is transmitted between generations with high fidelity, the epigenetic layer is sometimes erased between generations and sometimes not. To use a computer hardware analogy, the genetic layer is the non-volatile memory (hard disk) and the epigenetic layer is a semi-volatile memory (RAM). Darwinian evolution can operate on the epigenetic layer just as it can the genetic. The genetic layer is used to respond to long-term evolutionary pressures, and the epigenetic layer can be used to respond more flexibly to short-term evolutionary pressures. The epigenetic layer is not susceptible to Muller’s ratchet as is the genetic layer.

      • gcochran9 says:

        I used a word you evidently do not know: ‘evidence’. Look it up.

      • genetiker says:

        ZG: “You should consider epigenetics.”
        You: “There’s no evidence for Lamarckian inheritance.”
        Me: “Non sequitur.”

      • gcochran9 says:

        I disagree. Make a case.

      • RS-prime says:

        Strictly speaking it was a non-sequitur, but as has been fairly clear from context, Cochran is talking about germline transfer of salient epigenetic influence.

        I don’t think he denies that you can get certain breeds of rabbits or maize to stably change color across generations, or whatever. The question is, is that sort of thing is limited to a relative few phenomena of low salience — or might it in fact be, as you have lightly implied, meat-and-potatoes bio.

      • Zundblack Gesdorkin says:

        Google “PTSD and epigenetics”
        Then Google “PTSD and IQ”

        Alternatively, just Google “Autism and trains” (presumably you know enough about the last two centuries of history to not have to Google “Railroad Boom”)

    • Greying Wanderer says:

      “Keep ignoring epigenetics. You’ll go far.”

      Is the sudden outburst of epigenetics anything to do with the internet making a few cracks in the genetics is bunk wall?

  3. kjmtchl says:

    Visscher’s analyses may also be tracking mutational load, rather than implicating common variants as functional per se. They use common variants merely to map how closely related people are in the population. They show people who are more closely related are more similar to each othe in height, IQ and other traits. The more markers they use the more variance in the traits they can explain. In my opinion, this could be simply giving a better estimate of cryptic relatedness, which is indexing similarity in mutational load, rather than implying more and more common variants are directly functionally involved.

    • gcochran says:

      To an extent, yes. Visscher knows this. A recent, strongly deleterious mutation wouldn’t be old enough to show up in those calculations. In the limit, imagine a significantly bad mutation you got from your grandfather. Genetic similarity to distantly related people won’t predict its effects on you, because they simply don’t have it. It will, though, show up in a family heritability analysis. A denovo mutation, from your father, won’t even show up there – which means that even family studies miss some of the genetic influence.

      As stuff gets older (which means it can only be slightly deleterious) SNPs should eventually start to pick it up.

      The simplest way for a variant to get that old is if it is fitness-neutral, some kind of tradeoff.. Or only slightly deleterious, say 10-4.

  4. dave chamberlin says:

    “higher IQ is good, so why should variants of it ever be common.”
    Good? Lets replace that word with fitness advantage and now we see that higher IQ has all kinds of drawbacks. I was joking with my nephew a PHD in mathematics that he was altogether too normal and he responded that it wasn’t a joke at all. He is very normal and that makes him an oddball. When he is sitting in a room full of his peers he breaks down the crowd this way, one third of them are immediately recognizable as off socially, the next third will expose their weirdness if you hang with them for a day or two, and only the last third are normal. Now throw us back in time a century or two and having the mind capable of being a mathematician would be a considerably larger fitness disadvantage. I’m a happy daydreamer thanks to my intelligence, throw me back in time and make me a subsistence farmer and my kids are going to starve. So higher IQ is best understood as an asset to a larger population if and only if it is a small percentage of the group which is exactly what it is.

    • gcochran says:

      The situation you describe exists. Professional mathematicians are crazier than average, if you define crazy in terms of behaviors that would on average have had low Darwinian fitness in the past. And you’d be crazy to define it any other way.

      However, I do not think that this craziness is a consequence of high IQ, at least not much. I think that professional-grade mathematicians have to be smart, but being obsessed with math helps – and that’s obviously crazy.

      • greg kai says:

        IQ higher than average has been a fitness disadvantage recently, at least in the west, as shown by all the natality/IQ statistics….It has not been so in the past, but I wonder if this is so only for moderately high IQ? Do really high IQ, maybe the 1% top ones to give a example, has ever been a fitness advantage? Not so sure about that…

      • Matt says:

        The trait “obsessed with maths” rather than “obsessed (on a conscious or “unconscious” level) with increasing my fitness” I would think would be dependent on IQ (that is, more likely to manifest at higher IQ).

        People with no ability to understand maths (or whatever arcana that can become an obsession that distracts from the normal business of survival and reproductive success) would not become obsessed with it.

        That is to say, IQ is a trait which contributes to the development of intellectual interest traits which distract from reproduction, even if it is itself fitness improving (or neutral). Of course, there are other obsessions which the lower IQ may develop, but those do not seem to constitute distractions from reproduction to the same extent.

  5. nooffensebut says:

    Common SNPs account for half, but common CNVs and VNTRs count for nothing because…?

    • JL says:

      There’s an upcoming paper by Ian Deary et al. on CNVs and IQ in PLOS One. I’d guess they found little or nothing because it’s published in PLOS One.

    • Imprint says:

      http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0016339

      “Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77) had been administered the Wechsler Abbreviated Scale of Intelligence (WASI). After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = −.30, p = .01).”

  6. Mike Johnson says:

    Greg- you note that you don’t have much faith in current personality metrics. I feel similarly.

    I’d suggest that most of the variation in personality and cognitive style can be traced to variation in two things:
    1. linkages between brain regions (‘brain regions that fire together, wire together’), and
    2. general degree of signal leakage between regions (of which synethesia is the most famous symptom).

    Here’s my writeup on how I’d measure and map these things, if this sounds interesting.
    http://opentheory.net/2011/08/research-idea-tms-sonar/

  7. magnus says:

    What do you think of the theory that there might be some genes that confer higher fertility but also a higher chance of having homosexual offspring? Does the math not add up considering how many homosexuals there are? would we have found some corresponding genes by now but have not?

    I know your theory about childhood infection, and find it very interesting, and the idea that we might some day be able to “cure” homosexuality, weird and amusing.

  8. teageegeepea says:

    “one-third for schizophrenia”
    I recall earlier you noted that schizophrenics tend to be born during the winter, and that could be evidence of a pathogenic cause. Do those genetic results reduce your confidence in that theory?

    I recall n/a posting the abstract of a paper that tried to find some genetic indicators of homosexuality. None were found.

  9. Pingback: linkfest – 12/16/12 « hbd* chick

  10. o_o – I searched and found it. Thanks for the post. Mike McLen

  11. JayMan says:

    Dr. Cochran, have you seen this paper?

    Apparently, rare exonic variants were found not to be associated with low IQ:

    The total burden of rare, non-synonymous exome genetic variants is not associated with childhood or late-life cognitive ability

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