TY - JOUR
T1 - Polygenic signal for symptom dimensions and cognitive performance in patients with chronic schizophrenia
AU - Xavier, Rose Mary
AU - Dungan, Jennifer R.
AU - Keefe, Richard S.E.
AU - Vorderstrasse, Allison
N1 - Funding Information:
Data were obtained from the NIMH Repository and Genomics Resource (RGR). Dataset Identifier: NIMH Study 17, Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-schizophrenia trial. The principal investigators of the CATIE trial were Jeffrey A. Lieberman, M.D., T. Scott Stroup, M.D., M.P.H., and Joseph P. McEvoy, M.D. The CATIE trial was funded by a grant from the National Institute of Mental Health ( N01 MH900001 ) along with MH074027 (PI PF Sullivan). Genotyping for the CATIE trials were funded by Eli Lilly and Company . This manuscript reflects the views of the authors and may not reflect the opinions or views of the NIMH or of the submitters submitting original data to NIMH RGR.
Funding Information:
This work was supported in part by a doctoral training grant to RX by the Robert Wood Johnson Foundation Future of Nursing Scholars program (project number 72099 ).
Publisher Copyright:
© 2018
PY - 2018/6
Y1 - 2018/6
N2 - 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 (n = 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 (R2 = 0.007, p = 0.029, empirical p = 0.029) and negative symptoms at PT of 1e-07 (R2 = 0.005, p = 0.047, empirical p = 0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive (p-threshold 0.01, R2 = 0.007, p = 0.013, empirical p = 0.167) and negative symptoms (p-threshold 0.1, R2 = 0.012, p = 0.004, empirical p = 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.
AB - 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 (n = 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 (R2 = 0.007, p = 0.029, empirical p = 0.029) and negative symptoms at PT of 1e-07 (R2 = 0.005, p = 0.047, empirical p = 0.048). For models that additionally controlled for neurocognition, best fit PRS predicted positive (p-threshold 0.01, R2 = 0.007, p = 0.013, empirical p = 0.167) and negative symptoms (p-threshold 0.1, R2 = 0.012, p = 0.004, empirical p = 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.
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U2 - 10.1016/j.scog.2018.01.001
DO - 10.1016/j.scog.2018.01.001
M3 - Article
AN - SCOPUS:85041578619
SN - 2215-0013
VL - 12
SP - 11
EP - 19
JO - Schizophrenia Research: Cognition
JF - Schizophrenia Research: Cognition
ER -