More Information on NOS1 Gene Variant & IQ

The study which was an international collaboration with researchers from the Universities of Cardiff and Munich, was led by TCD researchers Dr Gary Donohoe, Dr Aiden Corvin, Dr Derek Morris, and Professor Michael Gill of the NRG and Department of Psychiatry, TCD and funded by Science Foundation Ireland. __InSciences

Scientists have known that human intelligence is between 50% and 80% heritable. The difficulty has been in identifying the multiple gene variants accounting for differences in cognitive potential. If this particular NOS1 variant can be proven to account for as much as 5 IQ points difference in IQ, it is likely that other gene variants will be shown to contribute to significant IQ differences.

Commenting on these findings Dr Gary Donohoe said: “Although the genetics of human intelligence has been more widely studied than any other human trait, pinning down the specific molecular variants involved has been slow, probably due to the complexity of IQ and the large number of variants involved. While further studies will be required to determine the true size of NOS1’s effect on human cognition, these data support the view that some genes may affect both cognition and risk for psychiatric illness. This is important not just for understanding the biological basis for cognition and psychiatric illness but also for developing new treatment targets for these disorders.” _InSciences

Single genes are not the holy grail for cognitive geneticists. It is the genetic interaction of multiple genes working together which will eventually be shown to cause persistent and significant population group differences in IQ.

Objective To investigate whether a potential schizophrenia risk single-nucleotide polymorphism (rs6490121) identified in a recent genome-wide association study negatively influences cognition in patients with schizophrenia and healthy control subjects.


Design A comparison of both cases and controls grouped according to NOS1 genotype (GG vs AG vs AA) on selected measures of cognition in 2 independent samples. We tested for association between NOS1 rs6490121 and cognitive functions known to be impaired in schizophrenia (IQ, episodic memory, working memory, and attentional control) in an Irish sample. We then sought to replicate the significant results in a German sample.


Setting Unrelated patients from general adult psychiatric inpatient and outpatient services and unrelated healthy volunteers from the general population were ascertained.


Participants Patients with DSM-IV–diagnosed schizophrenia and healthy control subjects from independent samples of Irish (cases, n = 349; controls, n = 230) and German (cases, n = 232; controls, n = 1344) nationality.


Results A main effect of NOS1 genotype on verbal IQ and working memory was observed in the Irish sample where the homozygous carriers of the schizophrenia risk G allele performed poorly compared with the other genotype groups. These findings were replicated in the German sample, again with the GG genotype carriers performing below other genotype groups. Post hoc analysis of additional IQ measures (full-scale and performance IQ) in the German sample revealed that NOS1 GG carriers underperformed on these measures also.


Conclusions NOS1 is associated with clinically significant variation in cognition. Whether this is a mechanism by which schizophrenia risk is increased (eg, via an influence on cognitive reserve) is yet to be confirmed. _ArchGenPsych

It is important to point out that persons homozygous for NOS1 G allele (GG) tested lower on verbal IQ and working memory. In the future it is likely that gene variants -- or combinations of multiple gene variants -- will be found to confer positive cognitive benefits compared to controls.

As soon as the larger picture of cognitive genetics becomes clearer, potential  genetic therapies to improve cognitive functioning should be developed. It is likely that such therapies would be more effective if implemented as early as possible in brain development, but perhaps not. The magnitude of improvement in cognition for adult brains may well make gene therapies worthwhile in the future.

The only road to true cognitive egalitarianism is to better understand cognitive differences. As soon as we sweep away all the PC crap, that task can be carried out more expeditiously.