Background
A strategy to improve genetic studies o
f schizophrenia involves the use o
f endophenotypes. In
formation on overlapping genetic contributions among endophenotypes may provide additional power, reveal biological pathways, and have practical implications
for genetic research. Several cognitive endophenotypes, including intelligence, are likely to be modulated by overlapping genetic in
fluences.
Methods
We quantified potential genetic and environmental correlations among endophenotypes for schizophrenia, including sensorimotor gating, openness, verbal fluency, early visual perception, spatial working memory, and intelligence, using variance component models in 35 patients and 145 relatives from 25 multigenerational Dutch families multiply affected with schizophrenia.
Results
Significant correlations were found between spatial working memory and intelligence (.45), verbal fluency and intelligence (.36), verbal fluency and spatial working memory (.20), and early visual perception and spatial working memory (.19). A strong genetic correlation (.75) accounted for 76 % of the variance shared between spatial working memory and intelligence. Significant environmental correlations were found between verbal fluency and openness (.50) and between verbal fluency and spatial working memory (.58). Sensorimotor gating and openness showed few genetic or environmental correlations with other endophenotypes.
Conclusions
Our results suggest that intelligence strongly overlaps genetically with a known cognitive endophenotype for schizophrenia. Intelligence may thus be a promising endophenotype for genetic research in schizophrenia, even though the underlying genetic mechanism may still be complex. In contrast, sensorimotor gating and openness appear to represent separate genetic entities with simpler inheritance patterns and may therefore augment the detection of separate genetic pathways contributing to schizophrenia.
