Researchers report that polygenic scores derived from one well-characterized cohort of schizophrenia patients correspond to clinical diagnostic categories in another.
They believe that the findings are “congruent with an underlying, continuous liability distribution” and represent “preliminary, molecular validation of a common genetic basis for the schizophrenia spectrum disorders.”
Kenneth Kendler (Virginia Commonwealth University School of Medicine, Richmond, USA) and team constructed a polygene score using published results from the Psychiatric Genome-Wide Association Studies Consortium and applied it to participants of the Irish Study of High Density Schizophrenia Families (ISHDSF) study.
A total of 843 ISHDSF participants were included in the analysis, and their individual polygene scores increased according to how narrow their diagnoses were; in other words, how close they were to having “pure” schizophrenia.
The average polygene score was 1.59 in the narrow diagnostic category, which included schizophrenia, poor-outcome schizoaffective disorder, and simple schizophrenia, the team reports in Schizophrenia Bulletin. This was significantly higher than the scores for patients in all other diagnostic categories.
“The observed pattern is consistent with that expected under the hypothesis of the schizophrenia spectrum with the narrow category having the highest score and the score decreasing in a nearly monotonic function across the other diagnostic categories,” say the researchers.
The intermediate category included diagnoses such as schizotypal personality disorder, atypical psychosis, and good-outcome schizoaffective disorder. The average polygene score for people in this diagnostic category was 1.47, similar to the 1.48 seen for people in the broad/very broad category, which included disorders such as psychotic affective illness, schizoid personality disorder, major depression, and alcohol dependence.
The polygene score was lower again in family members with no psychiatric diagnosis, at 1.32, but this was still significantly higher than the score of 0.96 seen for 1794 controls.
“As would be expected for any reasonable model of genetic transmission, individuals who are unaffected but close relatives of multiple individuals with schizophrenia or schizophrenia spectrum disorders are at an elevated genetic risk,” comment Kendler et al.
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