Posts Tagged ‘Intelligence’


Don’t worry about your general cognitive ability genes. Otherwise, check out this study led by Drs. Joe Trampush and Anil Malhotra from the Feinstein Institute showing that the less frequent and non-ancestral (A) alelle of rs1906252 was associated with higher Spearman’s General Intelligence (g-factor) scores.  This SNP sits 700 kilobases upstream of a putative ubiquitin ligase subunit (FBXL4) connected to severe psychomotor retardation. Loss-of-function in other ubiquitin ligase subunits have also been implicated in mental retardation.

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The “T” allele of rs1378810 in your DNAJC13 gene has been associated with a slight benefit (less than 0.4% variance) in general cognitive ability. You can check your 23andMe profile.*  What? You’re a TT? Ooooh … nobody is impressed. But let’s not make light of our DNAJ genes just yet.

Consider the critical role of DNAJC5, a so-called cysteine-string protein (because it encodes a protein with an array of cysteine residues). This protein helps synaptic vesicles fuse and un-fuse so that your neurons can release and re-cycle tiny packets of neurotransmitters – which is how neurons send signals to one another. Yeah, vesicle fusion is really important … and is happening like a quadriillion times right now in your brain.

Mutations in the cysteine string of DNAJC5 have been associated with Huntington’s disease.

[artwork credit]

*Interpreting 23andMe data here can be confusing because 23andMe lists an A or T as possible alleles but one isn’t always sure which strand the research literature refers to and if that strand is the same strand that 23andMe is reading from. Luckily SNPedia points out that an rs1378810 TT is in tight linkage disequilibrium with rs2133692 TT (T or C alleles) so you can check this genotype on 23andMe to infer your rs1378810 genotype. My 23andMe profile says AA at rs1378810 and TT at rs2133692, so I think I have the slightly beneficial TT genotype … but I’m really not sure. Confused? Me too. But like the research suggests, this genotype really doesn’t add much to one’s general cognitive ability.

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Enjoyed the August 2011 Neuropod(cast) on the topic of genetics and intelligence.  There is no mention of a major “intelligence gene”  (the author suggests there should be, rather, hundreds of very weak, small-effect genetic factors) but the author does point to their finding of a gene FNBP1L  that plays a role in the regulation of actin polymerization.  Why might the polymerization of actin matter?  The video below from Tom Bartol and colleagues shows just how wildly intertwined and elaborate synaptic connections can be.  The formation of this synaptic spaghetti is dependent on actin polymerization!  Mo’ spaghetti, mo’ smarts?

More on genes and intelligence here and here.


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Just a pointer to onetime University of Edinburgh Professor C.H. Waddington’s 1972 Gifford Lecture on framing the genes vs. environment debate of human behavior.  Although Waddington is famous for his work on population genetics and evolutionary change over time, several of his concepts are experiencing some resurgence in the neuroimaging and psychological development literatures these days.

One term, CHREOD, combines the Greek word for “determined” or “necessary” and the word for “pathway.” It describes a system that returns to a steady trajectory in contrast to homeostasis which describes a system which returns to a steady state.  Recent reviews on the development of brain structure have suggested that the “trajectory” (the actual term “chreod” hasn’t survived) as opposed to any specific time point is the essential phenotype to use for understanding how genes relate to psychological development.  Another term, CANALIZATION, refers to the ability of a population to produce the same phenotype regardless of variability in its environment or genotype.  A recent neonatal twin study found that the heritability of grey matter in neonatal humans was rather low.  However it seems to then rise until young adulthood – as genetic programs presumably kick-in – and then decline again.  Articles by neurobiologist Jay N. Giedd and colleagues have suggested that this may reflect Waddington’s idea of canalization.  The relative influence of genes vs. environment may change over time in ways that perhaps buffer against mutations and/or environmental insults to ensure the stability and robustness of functions and processes that are both appropriate for survival and necessary for future development.  Another Waddington term, EPIGENETIC LANDSCAPE, refers to the limitations on how much influence genes and environment can have on the development of a given cell or structure.  Certainly the environment can alter the differentiation, migration, connectivity, etc. of neurons by only so much.  Likewise, most genetic mutations have effects that are constrained or compensated for by the larger system as well.

Its amazing to me how well these evolutionary genetic concepts capture the issues at the nexus of of genetics and cognitive development.  From his lecture, it is clear that Waddington was not unaware of this.  Amazing to see a conceptual roadmap laid out so long ago.  Digging the book cover art as well!

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English: Visualization of a DTI measurement of...
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Have you ever had your butt kicked by a 12-year old girl?  OK, maybe when you were an 8-year old boy perhaps – but I mean as a grown up.  Its a humbling experience.  I know.  For once back in college, I sat for a math contest and was amazed by a young girl who was able to answer each question more quickly and accurately than anyone else (other college students) in the room.

How did she do it?  What was different about her brain than mine (illicit substances aside)?  Now, as a parent of children who will, themselves, soon start sitting for exams and contests – wouldn’t I like to know.  Might I perchance endow my children with brain power?  Not likely I imagine, but what is brain power anyway? and what is it about the brain that makes some people perform better in general intelligence assessments?  In their new research article, Genetics of Brain Fiber Architecture and Intellectual Performance [doi: 10.1523/jneurosci.4184-08.2009], Paul Thompson’s team of neurobiologists explore this longstanding question.

In this article, the team asks whether the white matter of the brain (the glial cells that ensheath neuronal axons) might be both heritable and correlated with measures of intelligence.  To measure white matter integrity, the team uses an imaging method known as diffusion tensor imaging (DTI).  It has been shown previously that measures of intelligence are correlated with white matter integrity – presumably because white matter serves as a kind of insulation that speeds up the transmission of action potentials  and thus facilitates interhemispheric communication and other long-range forms of neural network processing.  The team found that white matter integrity was correlated with performance on intelligence assessments in brain regions such as the cingulum, callosal isthmus, corona radiata, internal capsule and other regions.  By imaging 23 pairs of identical and 23 pairs of fraternal twins, the team also found many regions in the brain where white matter integrity was under more than 50% genetic control – particularly in the parietal lobe.  Lastly, the team found that in many of these regions, the correlation between white matter integrity and intelligence could be explained by the same genes.

Amazing research findings indeed, that points to where in the brain and what type of physiological processes are related to efficient brain function.

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Digital mock-up of human evolution display for...Image by Colin Purrington via Flickr

Just piling on to the many comments on today’s NY Times profile of David Goldstein who justifiably points out a dearth of whole-genome-snp-scanning success. One interesting debate is whether natural selection had anything to do with expunging the much sought-after (impossible to find) deleterious, disorder-promoting variants (he suggests yes) which means that whilst separate human cultures adapted to separate climate, predators, diets etc. one might expect to identify separate genetic variants that define racial or cultural subgroups (he says no). Huh?

According to the article, Goldstein “says he thinks that no significant genetic differences will be found between races because of his belief in the efficiency of natural selection. Just as selection turns out to have pruned away most disease-causing variants, it has also maximized human cognitive capacities because these are so critical to survival. “My best guess is that human intelligence was always a helpful thing in most places and times and we have all been under strong selection to be as bright as we can be.””

We have a free and open article describing the relationship of a common variant in the COMT gene with human intelligence, which is also supported by a recent meta-analysis on COMT. These findings certainly do not refute Dr. Goldstein’s conclusions, but rather make me wonder why the common valine/methionine variant in COMT might exert a tiny, but measurable, effect on intelligence. Balancing selection possibly ?

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inside my brain
Image by TheAlieness GiselaGiardino²³ via Flickr

Every student can recall at least one stereotypical professor who – while brilliant – kept the students amused with nervous and socially inept behavior. Let’s face it, if you’re in academia, you’re surrounded by these – uh, nerds – and, judging by the fact that you are reading (not to mention writing) this blog right now – probably one of them. So, its natural to ask whether there might be a causal connection between emotionality, on the one hand, and cognitive performance on the other. Research on the neuromodulator serotonin shows that it plays a key role in emotional states – in particular, anxiety. Might it exert effects on cognitive performance ? In their paper, “A functional variant of the tryptophan hydroxylase 2 gene impacts working memory: A genetic imaging study“, (DOI: 10.1016/j.biopsycho.2007.12.002) Reuter and colleagues use a genetic variation a G to T snp (rs4570625) in the tryptophan hydroxylase 2 gene, a rate limiting biosynthetic isoenzyme for serotonin to evaluate its effect on a cognitive task. They ask subjects (who are laying in an MRI scanner) to perform a rather difficult cognitive task called the N-back task where the participant must maintain a running memory queue of a series of sequentially presented stimuli. Previous research shows that individuals with the GG genotype show higher scores on anxiety-related personality traits and so Reuter and team ask whether these folks activate more or less of their brain when performing the N-back working memory task. It turns out that the GG group showed clusters of activity in the frontal cortex that showed less activation than the TT group. The authors suggest that the GG group can perform the task using by recruiting less of their brains – hence suggesting that perhaps there just might be a genetic factor that accounts for a possible negative correlation between efficient cognitive performance and emotionality.

My 23andMe profile shows a GG here – nerd to the hilt – what will I use the rest of my PFC for ? Something else to worry about.

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