Population genetic studies may have limited role in schizophrenia

By Eleanor McDermid, Senior medwireNews Reporter

Studying the genetics of people in the general population who have psychotic experiences is unlikely to reveal useful information about schizophrenia, say researchers.

Stanley Zammit (Cardiff University, UK) and colleagues found that a polygenic score strongly linked to schizophrenia was not associated with psychotic experiences among 3483 adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort.

This indicates “that the genetic architecture of psychotic experiences in the general population is not likely to be comparable to that underlying schizophrenia,” the team writes in Schizophrenia Bulletin.

“The implication of this is that while samples may be easier to collect, genetic studies of psychotic experiences are unlikely to aid understanding of the genetic etiology of schizophrenia, or, at the very least, will be substantially underpowered compared to equivalent-sized samples of individuals with this disorder.”

Zammit et al used a polygenic score based on data from the Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ). But this score, which indicates genetic vulnerability to schizophrenia, was no higher in the 424 adolescents who reported definite psychotic experiences in the Psychosis-Like Symptoms interview than in those who did not.

“This is contrary to expectations if the presence of psychotic experiences offers a strong indicator of underlying genetic risk,” says the team.

Indeed, the evidence tended to suggest the opposite effect, with three of the 17 single nucleotide polymorphisms that had the strongest association with schizophrenia seeming to have a significant protective effect against psychotic experiences among the adolescents.

“It would be surprising if genetic factors associated with schizophrenia risk do not have any influence at all on incidence of psychotic experiences in the general population,” say the researchers.

However, they note that although the polygenic score had a very strong statistical association with schizophrenia risk in the validation studies, it in fact explained less than 5% of the variance, suggesting that a polygenic risk score may never prove to be an accurate predictive tool.

The team suggests that evaluating other psychosis-related phenotypes, such as neurocognition and neuroimaging, in the general population could prove more informative than genetic studies.

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