Saturday, 19 September 2015

Genius? Avoid rare functional genes

 

For some time now I have been waiting for the results of the genetic analysis of genius, even while knowing that intelligence is heritable, but created by many, many genes of small effect. So, needle, haystack, and the needles aren’t just for sewing, but do other things as well.

However, on the good side, I believe that Plomin will nail the genes for intelligence before they nail him. This paper brings us a step closer to understanding the genetic underpinnings of exceptionally high intelligence, suggesting it happens when some intelligence damaging genes are not present. The team have looked at only the subset of DNA that encodes proteins,  because mutations in those sequences are much more likely to have severe consequences.

Image result for robert plomin king's college london

https://kclpure.kcl.ac.uk/portal/robert.plomin.html

A GENOME-WIDE ANALYSIS OF PUTATIVE FUNCTIONAL AND EXONIC VARIATION ASSOCIATED WITH EXTREMELY HIGH INTELLIGENCE Robert Plomin1 , Sarah L. Spain2 , Inti Pedroso2 , Neli Kadeva2 , Mike B. Miller3 , William G. Iacono3 , Matt McGue3 , Evie Stergiakouli4 , George Davey Smith4 , Martha Putallaz5 , David Lubinski6 , Emma L. Meaburn7 , Michael A. Simpson2

1 Institute of Psychiatry, Psychology & Neuroscience; King’s College London, robert.plomin@kcl.ac.uk.

2 Division of Genetics and Molecular Medicine, King’s College London.

3 Department of Psychology University of Minnesota.

4 MRC Integrative Epidemiology Unit University of Bristol.

5 Duke University Talent Identifcation Program Duke University.

6 Department of Psychology and Human Development Vanderbilt University. 7 Department of Psychological Sciences Birkbeck, University of London.

Although individual differences in intelligence are highly heritable, molecular genetic analyses to date have had limited success in identifying specific loci responsible for its heritability. The present study is the first to investigate exome variation in individuals of extremely high intelligence. Under the quantitative genetic model, sampling from the high extreme of the distribution should provide increased power to detect associations.

We performed a case-control association analysis with 1,409 individuals drawn from the top 0.0003 (IQ > 170) of the population distribution of intelligence and 3,253 unselected population-based controls. Our analysis focused on putative functional exonic variants assayed on the Illumina Human Exome BeadChip. We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence. Moreover, no significant associations were found for multiple rare alleles within individual genes.

However, analyses using genome-wide similarity between unrelated individuals (Genome-wide Complex Trait Analysis) indicate that the genotyped functional protein-altering variation yields a heritability estimate of 17.4% (SE 0.017) based on a liability model. In addition, investigation of nominally significant associations revealed fewer rare alleles associated with extremely high intelligence than would be expected under the null hypothesis.

A common theme emerging from genetic studies of intelligence, similar to all complex traits and common disorders, is its highly polygenic nature with its heritability explained by many variants of small effect. While the unique extreme sampling design used in the current study provides improved power to detect associations in certain situations it has also provided challenges for direct replication. Nevertheless, the evidence for the contribution of protein-altering variants to the heritability of intelligence and the evidence that rare functional alleles are detrimental to intelligence provides a framework for defining the role of individual rare alleles.

13 comments:

  1. I'm glad you're covering this conferences for those of us who couldn't afford to go!

    "We did not observe any individual protein-altering variants that are reproducibly associated with extremely high intelligence and within the entire distribution of intelligence."

    They're looking for love in all the wrong places. I seriously doubt protein-altering genes are where we're going find most of our money. Likely, as Steve Hsu has pointed out, it is the regulatory loci where the good stuff will be found. In any case, I suspect rapid progress in the next 10 years as soon as researchers learn from all the dead ends they've run into.

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  2. Is there any evidence that (i) you need an IQ > 170 to be a genius, or (ii) that everyone with an IQ > 170 is a genius? Isn't this IQ-170 business just altering what we mean when we say that Shakespeare or Rembrandt or Darwin was a genius?

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    1. I think an element of not giving a **** ness is probably required.

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    2. If you define a genius as someone who has an IQ over a certain number, let's say 140, then by definition a person with a 170 IQ is a genius. Since we never tested Shakespeare, Rembrandt or Darwin we can only guess at their intelligence. Conversely, do all people who have high IQs produce works of art, literature and science that resonate through the ages? No, they don't.

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    3. "If you define a genius as someone who has an IQ over a certain number": but why on earthy would you do that? "Genius" already has an existing and different meaning.

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  3. "suggesting it happens when some intelligence damaging genes are not present"

    interesting

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  4. I hope someone starts to look at the mothers. If early development is critical some of the critical genes may be in the mothers.

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  5. How do you find over 1400 people with IQs over 170 when there are no well-normed tests with ceilings over 160? (And none accurate over 150 due to subtest ceilings.) If you do somehow manage this feat, you would have vast numbers of people who scored in the 160s, certainly enough to realize that the normal distribution does not apply that far out and that the corresponding rarity number (0.0003 [percent]) is wrong. (I believe it was Cyril Burt who first noticed the leptokurtosis of the intelligence distribution. Log-normal and Pearson type IV distributions have been proposed for intelligence, but so far as I know the high-range data hasn't been good enough so far to decide the matter, though Burt favored the Pearson type IV distribution.)

    These apparent errors make me extremely dubious about the correctness of the more complicated analysis of the rest of this paper.

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    1. I haven't got the inclusion criteria to hand, but from memory they go for very high scores on demanding mathematical and reasoning tasks. Agree that conventional IQ testing is not the best way to find such people. A list of the Senior Wranglers suffices.

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    2. The list of Senior Wranglers excludes Clerk Maxwell!

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    3. His one mistake was to turn down going to Cambridge. Only by being examined there could he become a Senior Wrangler. However, he is high in the pantheon nonetheless.

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    4. As an undergraduate, that is. Later he was looking for a Fellowship.

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  6. Love is an ice cream sundae, with all the marvelous coverings. Sex is the cherry on top. Hey, i am looking for an online sexual partner ;) Click on my boobs if you are interested (. )( .)

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