Genetic Overlap between General Cognitive Function and Schizophrenia: A Review of Cognitive GWASs

Abstract

General cognitive (intelligence) function is substantially heritable, and is a major determinant of economic and health-related life outcomes. Cognitive impairments and intelligence decline are core features of schizophrenia which are evident before the onset of the illness. Genetic overlaps between cognitive impairments and the vulnerability for the illness have been suggested. Here, we review the literature on recent large-scale genome-wide association studies (GWASs) of general cognitive function and correlations between cognitive function and genetic susceptibility to schizophrenia. In the last decade, large-scale GWASs (n > 30,000) of general cognitive function and schizophrenia have demonstrated that substantial proportions of the heritability of the cognitive function and schizophrenia are explained by a polygenic component consisting of many common genetic variants with small effects. To date, GWASs have identified more than 100 loci linked to general cognitive function and 108 loci linked to schizophrenia. These genetic variants are mostly intronic or intergenic. Genes identified around these genetic variants are densely expressed in brain tissues. Schizophrenia-related genetic risks are consistently correlated with lower general cognitive function (rg = −0.20) and higher educational attainment (rg = 0.08). Cognitive functions are associated with many of the socioeconomic and health-related outcomes. Current treatment strategies largely fail to improve cognitive impairments of schizophrenia. Therefore, further study is needed to understand the molecular mechanisms underlying both cognition and schizophrenia.

Jumping To Conclusions, General Intelligence, And Psychosis Liability: Findings From The Multi-Centre EU-GEI Case-Control Study

“…GWAS studies have found a significant genetic overlap between cognition and schizophrenia [18][19][20] , and a recent study by Toulopoulou et al 21 showed that the variance in schizophrenia liability explained by PRS was partially mediated through cognitive deficit.…”

Polygenic Risk Scores Shed Light on the Relationship between Schizophrenia and Cognitive Functioning: Review and Meta-Analysis

“…In conclusion, accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction and reciprocally [22,37]. Other data indicate a strong and specific genetic link between cognitive impairment and loss of functioning [36], yet with few data to date.…”

“…The g factor represents the general cognitive function and is defined as a latent trait underlying shared variance across multiple subdomains of cognition. More details and a summary of GWAS of general cognitive function can be found in [22]. Some specific cognitive domains are also highly heritable [27].…”

Molecular Psychiatry: Trends and Study Examples

“…The influence of genetic markers in psychiatric traits is also subject of the review from Ohi and colleagues [19], which explored the genetic determinants of general cognitive function and how they overlap with schizophrenia. Lower general cognitive function has been repeatedly associated with a higher risk for schizophrenia, and a genetic risk may likely underlie this association.…”