Research supports polygenic phenotype in schizophrenia
medwireNews: Cumulative genetic risk for schizophrenia has been linked to impaired prefrontal brain activity, in findings that support an additive genetic risk model for a polygenic phenotype.
"A neural characterization of genetic risk could help to define system neuroscience models of schizophrenia," say Stefan Ehrlich (Dresden University of Technology, Germany) and team.
They add that if measuring cumulative genetic risk rather than single genes to predict intermediate phenotypes does prove to be advantageous in ongoing work, it may help to estimate the risk for schizophrenia in vulnerable populations.
The researchers genotyped 79 patients with schizophrenia and 99 mentally healthy controls for 41 single-nucleotide polymorphisms (SNPs) from 34 known risk genes for schizophrenia. From this, they calculated a genetic risk score (GRS) which combined the additive effects of the SNPs.
The risk genes, chosen according to the latest meta-analysis of genetic studies on schizophrenia, are involved in neurodevelopment, neurotransmitter systems, and other functions, such as cell adhesion, cell cycle, immune response, and transcription.
As reported in Schizophrenia Bulletin, there was a positive relationship between GRS and left dorsolateral prefrontal cortex inefficiency during working memory processing - "a widely acknowledged intermediate phenotype for schizophrenia," the researchers note.
Indeed, the GRS accounted for 3.6% of the total variance at the most activated dorsolateral prefrontal cortex locale, which corresponded to a significant coefficient of determination of 0.04.
The team adds that this association was not explained by symptom severity, population stratification, or differences in working memory performance.
"The fact that GRS was linked to brain function but not to task performance or symptom severity suggests that the GRS reflects unique genetic aspects of aberrant neural responses related to schizophrenia that are perhaps not well represented in the clinical or cognitive presentations of patients or high-risk individuals," Ehrlich et al explain.
They say that by studying many genes with small effects, they were able to detect the additive effects of these genes on different biological pathways, which in turn impinge on prefrontal cortical function but at a level undetectable in the behavior or symptomatology of an individual.
The researchers believe their findings bode well for "the validity of intermediate neural phenotypes suggesting that genetic effects are more clearly discerned through biological constructs than descriptions of complex behavior."
medwireNews (www.medwirenews.com) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2013
By Lucy Piper, Senior medwireNews Reporter