IL1RAPL1 Genotype & Intelligence

I’m kinda surprised that this paper, “A study on the correlation between IL1RAPL1 and human cognitive ability,” hasn’t made many waves in the press nor in the blogosphere. Aside from being controversial, it is a pretty fascinating study. But, I’m not completely shocked many have abstained from mentioning it… Like the genetics of race, the genetics of intelligence is a topic many researchers aren’t willing to bet their academic careers on. Why? Because, it has been source for some pretty knee-jerk reactions.

Don’t believe me?

Remember what James Watson said last fall? To save grace, I’m not gonna reiterate his words… But I will mention that the consequences of Watson’s commentary are rather unforgettable. He lost a very prestigious career, and ended his successful reign in science on a bad note. I’m not defending beliefs like Watson’s, especially because what he said was expressed as subjective, inflammatory conjecture more than anything else, but I am curious about looking into how genetic predispositions affect intelligence and cognition.

I’ve done some reading on the topic and started many discussions about this topic, bringing up the correlations of higher than normal intelligence and the higher than normal incidences for many genetic diseases (like Tay-Sachs and hemophilia) in in Ashkenzai Jews as a case study. Time and time again, discussions have been shunned down. I’ve wondered why and I’ve come to think that people just don’t want to engage in this train of thought because of the possible repercussions it has. I worry that it has more to do with being politically correct than anything else.

That all being said, I’m very excited to have stumbled across this current paper from Dienekes. I wouldn’t have found it if it weren’t for his post. As you can tell from the title, this paper focuses on a correlation between a gene and cognition in humans. Please note how the authors are all Chinese academics, seems like folk in China people aren’t afraid to research this topic.

Anyhoot, the gene of interest, IL1RAPL1, is believed to function in binding of a kinase to a receptor. On Monday, I took an exam on this subject, looking into all the known different signal transduction mechanisms and receptor kinases were a major part of the test. Kinases are special proteins, enzymes that phosphorylate other proteins. In most common terms, a phosphorylated protein is an active one. Receptor kinases span the membranes of cells and receive extracellular stimulus to activate intracellular proteins. L1RAPL1 is expressed in muscle and brain tissue.

Previous studies have shown that individuals who have deletions or inversions of L1RAPL1 have a form of mental retardation. This indicates an important signaling pathway involved in cognition is lost when L1RAPL1 is knocked out, which is what got this group of academics to hone in on L1RAPL1 as a gene linked to cognition. To date, there has not been an investigation on the impact of the alleic variants of L1RAPL1 on cognition, which is the scope of this paper. The paper specializes in looking at relationship of L1RAPL1 polymorphisms (two microsattelites and two SNPs) with intelligence in population of Chinese kids. They also extended this study by looking a the effects of the polymorpisms on rats.

In their sample, the L1RAPL1 of 332 children (50:50 male to female), aged 5-14 years old, was screened. The genotype of each child’s L1RAPL1 variant was identified using PCR. In the population, roughly 90% were heterozygotic in the DXS1218 microsattelite variant of L1RAPL1 . Microsattelites are simple repeats of nucleotides in a sequence of DNA, I outlined one way they come about here. The other microsattelite, DXS9896 was present as heterzygotic alleles in 87% of the kids.

Two SNPs are also looked at. 89% of the kids had an A nucleotide in the rs6526806 SNP, where the other 11% had a G. 42% of the kids had one version of the rs12847959 SNP, the other 58% had another version. The authors did not mention what effect these polymorphisms had on the gene, but did indicate they all fall in the intron of the gene — a non-coding region that is spliced out.

The kids were asked to take several cognitive tests that tested their memory, concentration, perception, and verbal abilities. Three of the polymorphisms listed above had effects on memory and concentration. Those that had longer DXS1218 microsattelite variants had lower IQ scores. Similarly, kids with longer DXS9896 mircosattelites also had lower IQ scores. One of the SNPs, rs12847959 showed that individuals that had the CC genotype in the SNP had higher IQ scores compared to those that had the CG genotype. The p-values for all were pretty strict, suggesting that the differences are statistically significant.

I find the results pretty cool. Those with longer introns seem to have reduced IQ scores. Those with a difference in 1 base pair also seem to have differences in IQ scores. Now, what do lower IQ scores have to do with intelligence? Can we say low IQ scores equal dumber people? Many people will say no. IQ tests have often been criticized for not being an adequate screens of intelligence, but they are one of the only ways to systematically and uniformly exam some degree of memory, concentration, perception, and verbal abilities. I find the use of them kinda flawed because the children screen in this study were from different ages, if they all came from the same age group, I would say there would be more structure. I know I was much more intelligent at age 14 than I was at age 5… my parents may disagree though.

I want to also outline that L1RAPL1 is one of the 8,000 or so genes expressed in the human brain, all of which have some function the brain and ultimately in cognition. Thus, intelligence is very much an epistatic trait and we can’t just say alleles of L1RAPL1 are the only player in determining cognitive abilities. Perhaps a wider genome wide association/linkage disequilibrium study will begin to identify all the genetic players affecting intelligence.

    GAO, X., XI, G., NIU, Y., ZHANG, S., FU, R., ZHENG, Z., ZHANG, K., LV, S., HE, H., XUE, M. (2008). A study on the correlation between IL1RAPL1 and human cognitive ability. Neuroscience Letters DOI: 10.1016/j.neulet.2008.03.084

9 thoughts on “IL1RAPL1 Genotype & Intelligence

  1. Totally outside this post but perhaps you may be able to help me Kambiz. I see a new Y-chromosome haplogroup, C6, has been recognised but I can find no information at all as to where it’s mainly found. Does anyone know?

    Regarding an intelligence gene. The problems seem to arise when people try to connect increased (or decreased)intelligence with a particular racial or cultural group. But so what if some paricular group is, on average, less intelligent (however we might manage to measure that) than some other group. Some members of either group will be less intelligent than members of the other group, others from each group will be more intelligent. Besides, does greater intelligence necessarily indicate superiority? I suspect the stress on regarding intelligence as a driving force during our evolution springs as much from the fact that research is done by academics as from any relationship to reality. Academics regard their own intelligence as important in their lives therefore, naturally enough, they expand the concept.

    Anyway the research you’ve provided us with here shows yet again that the action of genes is far from simple.

  2. I know I was much more intelligent at age 14 than I was at age 5… my parents may disagree though.

    But your IQ should be about the same, as it’s measured by “mental age” divided by real age. This is specially true if the IQ is only or mostly a product of genetic conditionants.

    Now, apart of the political correctness or the matter, there is another issue: we really understand intelligence poorly. IQ measures only logical abilities, not artistic, communicational, empathic or other aspects that also make up intelligence. Creativity is not measured, nor are reflexes. If taken in a second language you surely will score lower than in your maternal tongue, your education certainly matters too. If you suffered malnutrition as child certainly you are likely to have a lower IQ than if you were well fed. Global (and local) IQ seems to grow significatively every generation too. There’s a lot of uncertainty regarding intelligence and simplifying into IQ is certainly slippery terrain.

    Also this gene may be correlated with IQ but what about all the other factors that we don’t know about yet. There is surely more than just one gene involved in describing the complexity human brain, I’m sure. Having a gene is not in itself a guarantee that you’ll have the trait others get with it: often different genes or epigenetic factors may silence (or amplify, or otherwise alter) it.

    So it’s a complex issue. I perfectly understand that people is basically in the attiutude of “watch and see”. What is striking news now tomorrow may become rather irrelevant.

  3. As I see it the real problem is that what is being measured is not really intelligence, in the sense we usually give to that term. What’s being measured is “IQ,” which must be understood in strictly technical terms. And the fact that IQ is closely tied to the value system of one particular type of society makes all these findings particularly dubious. Another type of “IQ” test could be given — one that tests people’s ability to think quickly in the midst of changing situations or react efficiently to unexpected circumstances, etc. Or one that tests ones sensori-motor skills. Or one based on mechanical aptitude. And in each of these tests a completely different segment of the world population would most likely excell. I’m not saying that tests of this kind are pointless or misleading, just that the whole testing process has to be understood in a broader context. The way things stand at the moment, the tests are certainly “fixed” in such a way that people from cultures with a certain type of value system that favors a certain type of learning will always come out on top.

  4. I see a new Y-chromosome haplogroup, C6, has been recognised but I can find no information at all as to where it’s mainly found. Does anyone know?

    Karafet mentions New Guinea specifically.

    As I see it the real problem is that what is being measured is not really intelligence, in the sense we usually give to that term. What’s being measured is “IQ,” which must be understood in strictly technical terms.

    That’s the main criticism towards IQ. You may have a high IQ and be awful at music or diplomacy. It just measures your logical ability, that is certainly important but not the only important thing.

    Also mean IQ is not static, it seems to be increasing everywhere generation after generation. Either selection or education is working strongly there.

  5. I think Luis and Victor make some good points in saying that we don’t fully understand intelligence, and there’s good reason to be skeptical about IQ measures.

    Your point about the variable ages is also a valid one, IMO. Even if IQ is assumed to be constant as one grows older, I don’t think there’s any evidence for treating it as such. IQ is also dependent on socio-economic and cultural factors, so whatever is being measured is bound to be rather variable unless these other factors are controlled for.

    That said, I think there is good reason to believe that mental traits have at least some basis in genetics. Whether or not there is variability between different races should not affect how individuals are treated. While I think there is a strong biological component for most traits, I am strongly against passing judgement on someone based only their genes. For all we know, it may turn out that there is significant variability in mental abilities within races rather than between different races.

  6. “Please note how the authors are all Chinese academics, seems like folk in China people aren’t afraid to research this topic.”

    I don’t think political correctness has caught on in China yet!

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