Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia.
Schizophr Res Cogn
; 12: 11-19, 2018 Jun.
Article
em En
| MEDLINE
| ID: mdl-29552508
ABSTRACT
Genetic etiology of psychopathology symptoms and cognitive performance in schizophrenia is supported by candidate gene and polygenic risk score (PRS) association studies. Such associations are reported to be dependent on several factors - sample characteristics, illness phase, illness severity etc. We aimed to examine if schizophrenia PRS predicted psychopathology symptoms and cognitive performance in patients with chronic schizophrenia. We also examined if schizophrenia associated autosomal loci were associated with specific symptoms or cognitive domains. Case-only analysis using data from the Clinical Antipsychotics Trials of Intervention Effectiveness-Schizophrenia trials (nâ¯=â¯730). PRS was constructed using Psychiatric Genomics Consortium (PGC) leave one out genome wide association analysis as the discovery data set. For candidate region analysis, we selected 105-schizophrenia associated autosomal loci from the PGC study. We found a significant effect of PRS on positive symptoms at p-threshold (PT ) of 0.5 (R2â¯=â¯0.007, pâ¯=â¯0.029, empirical pâ¯=â¯0.029) and negative symptoms at PT of 1e-07 (R2â¯=â¯0.005, pâ¯=â¯0.047, empirical pâ¯=â¯0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive (p-threshold 0.01, R2â¯=â¯0.007, pâ¯=â¯0.013, empirical pâ¯=â¯0.167) and negative symptoms (p-threshold 0.1, R2â¯=â¯0.012, pâ¯=â¯0.004, empirical pâ¯=â¯0.329). No associations were seen for overall neurocognitive and social cognitive performance tests. Post-hoc analyses revealed that PRS predicted working memory and vigilance performance but did not survive correction. No candidate regions that survived multiple testing corrections were associated with either symptoms or cognitive performance. Our findings point to potentially distinct pathogenic mechanisms for schizophrenia symptoms.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
Schizophr Res Cogn
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Estados Unidos