A polygenic architecture of susceptibility to schizophrenia also modifies the neurocognitive performance in patients with schizophrenia, according to a collaborative research led by Dr. Wei J. Chen, a distinguished professor at National Taiwan University College of Public Health (Institute of Epidemiology and Preventive Medicine) and Dr. Shi-Heng Wang, an assistant professor at China Medical University (Graduate Institute of Biostatistics). The results have been published online by Genes, Brain and Behavior (doi: 10.1111/gbb.12401).
“Both neurocognitive deficits and schizophrenia are highly heritable,” said Dr. Chen, corresponding author of the paper, “and the genetic overlap between them has been observed in the general population. But we knew very little about the underlying genetic basis of this overlap.” To take advantage of the genome-wide association studies collected by the Psychiatric Genomics Consortium (PGC) on schizophrenia, the research team decided to derive the polygenic risk scores (PRS) from this GWAS database. They then calculated the scores in another independent sample of 1130 schizophrenia trios, who were recruited from Schizophrenia Trio Genomic Research in Taiwan (S-TOGET), led by principal investigators Dr. Ming T. Tsuang (University of California San Diego) and Dr. Stephen J. Glatt (SUNY Upstate Medical University) along with local Co-PIs Dr. Hai-Gwo Hwu (National Taiwan University Hospital) and Dr. Wei J. Chen. Each patient underwent neurocognitive evaluation on sustained attention using the Continuous Performance Test and executive function using the Wisconsin Card Sorting Test.
The team first assessed the replicability of PGC-derived susceptibility variants in this Han-Taiwanese data. According to Dr. Wang, first-author of the paper, “Schizophrenia PRS explained 0.2 percent in the variance of disease status in this Han-Taiwanese sample, and the score itself had a p-value of 0.05 for the association test with the disorder.”
The team then applied a structural equation model to construct the neurocognitive latent variable estimated from multiple neurocognitive indices. “Higher schizophrenia PRS was significantly associated with poorer neurocognitive performance, which explained 0.5 percent of the variance in schizophrenia patients,” says Dr. Wang. These findings indicated that the polygenic architecture of susceptibility to schizophrenia modifies the neurocognitive performance in schizophrenia patients.