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Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study.
- Source :
-
Psychological medicine [Psychol Med] 2020 Aug; Vol. 50 (11), pp. 1884-1897. Date of Electronic Publication: 2019 Aug 15. - Publication Year :
- 2020
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Abstract
- Background: First-degree relatives of patients with psychotic disorder have higher levels of polygenic risk (PRS) for schizophrenia and higher levels of intermediate phenotypes.<br />Methods: We conducted, using two different samples for discovery (n = 336 controls and 649 siblings of patients with psychotic disorder) and replication (n = 1208 controls and 1106 siblings), an analysis of association between PRS on the one hand and psychopathological and cognitive intermediate phenotypes of schizophrenia on the other in a sample at average genetic risk (healthy controls) and a sample at higher than average risk (healthy siblings of patients). Two subthreshold psychosis phenotypes, as well as a standardised measure of cognitive ability, based on a short version of the WAIS-III short form, were used. In addition, a measure of jumping to conclusion bias (replication sample only) was tested for association with PRS.<br />Results: In both discovery and replication sample, evidence for an association between PRS and subthreshold psychosis phenotypes was observed in the relatives of patients, whereas in the controls no association was observed. Jumping to conclusion bias was similarly only associated with PRS in the sibling group. Cognitive ability was weakly negatively and non-significantly associated with PRS in both the sibling and the control group.<br />Conclusions: The degree of endophenotypic expression of schizophrenia polygenic risk depends on having a sibling with psychotic disorder, suggestive of underlying gene-environment interaction. Cognitive biases may better index genetic risk of disorder than traditional measures of neurocognition, which instead may reflect the population distribution of cognitive ability impacting the prognosis of psychotic disorder.
- Subjects :
- Adult
Case-Control Studies
Endophenotypes
Europe
Female
Genetic Predisposition to Disease
Humans
Male
Middle Aged
Psychotic Disorders psychology
Risk Factors
Schizophrenic Psychology
Young Adult
Gene-Environment Interaction
Multifactorial Inheritance
Psychotic Disorders genetics
Schizophrenia genetics
Siblings
Subjects
Details
- Language :
- English
- ISSN :
- 1469-8978
- Volume :
- 50
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Psychological medicine
- Publication Type :
- Academic Journal
- Accession number :
- 31414981
- Full Text :
- https://doi.org/10.1017/S003329171900196X