Polygenic Risk Scores for Subtyping of Schizophrenia
Schizophrenia is a complex disorder with many comorbid conditions. In this study, we used polygenic risk scores (PRSs) from schizophrenia and comorbid traits to explore consistent cluster structure in schizophrenia patients. With 10 comorbid traits, we found a stable 4-cluster structure in two datas...
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doaj-9db418c04a974eb4a2f37c06f0ce436f2020-11-25T03:21:59ZengHindawi LimitedSchizophrenia Research and Treatment2090-20852090-20932020-01-01202010.1155/2020/16384031638403Polygenic Risk Scores for Subtyping of SchizophreniaJingchun Chen0Travis Mize1Jain-Shing Wu2Elliot Hong3Vishwajit Nimgaonkar4Kenneth S. Kendler5Daniel Allen6Edwin Oh7Alison Netski8Xiangning Chen9Nevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USANevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USANevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USADepartment of Psychiatry, University of Maryland, Baltimore, MD 21228, USADepartment of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USADepartment of Psychiatry, Virginia Commonwealth University, Richmond, VA 23298, USADepartment of Psychiatry and Behavioral Health, University of Nevada, Las Vegas, School of Medicine, NV 89102, USANevada Institute of Personalized Medicine, University of Nevada, Las Vegas, NV 89154, USADepartment of Psychiatry and Behavioral Health, University of Nevada, Las Vegas, School of Medicine, NV 89102, USA410 AI, LLC, Germantown, MD 20876, USASchizophrenia is a complex disorder with many comorbid conditions. In this study, we used polygenic risk scores (PRSs) from schizophrenia and comorbid traits to explore consistent cluster structure in schizophrenia patients. With 10 comorbid traits, we found a stable 4-cluster structure in two datasets (MGS and SSCCS). When the same traits and parameters were applied for the patients in a clinical trial of antipsychotics, the CATIE study, a 5-cluster structure was observed. One of the 4 clusters found in the MGS and SSCCS was further split into two clusters in CATIE, while the other 3 clusters remained unchanged. For the 5 CATIE clusters, we evaluated their association with the changes of clinical symptoms, neurocognitive functions, and laboratory tests between the enrollment baseline and the end of Phase I trial. Class I was found responsive to treatment, with significant reduction for the total, positive, and negative symptoms (p=0.0001, 0.0099, and 0.0028, respectively), and improvement for cognitive functions (VIGILANCE, p=0.0099; PROCESSING SPEED, p=0.0006; WORKING MEMORY, p=0.0023; and REASONING, p=0.0015). Class II had modest reduction of positive symptoms (p=0.0492) and better PROCESSING SPEED (p=0.0071). Class IV had a specific reduction of negative symptoms (p=0.0111) and modest cognitive improvement for all tested domains. Interestingly, Class IV was also associated with decreased lymphocyte counts and increased neutrophil counts, an indication of ongoing inflammation or immune dysfunction. In contrast, Classes III and V showed no symptom reduction but a higher level of phosphorus. Overall, our results suggest that PRSs from schizophrenia and comorbid traits can be utilized to classify patients into subtypes with distinctive clinical features. This genetic susceptibility based subtyping may be useful to facilitate more effective treatment and outcome prediction.http://dx.doi.org/10.1155/2020/1638403 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jingchun Chen Travis Mize Jain-Shing Wu Elliot Hong Vishwajit Nimgaonkar Kenneth S. Kendler Daniel Allen Edwin Oh Alison Netski Xiangning Chen |
spellingShingle |
Jingchun Chen Travis Mize Jain-Shing Wu Elliot Hong Vishwajit Nimgaonkar Kenneth S. Kendler Daniel Allen Edwin Oh Alison Netski Xiangning Chen Polygenic Risk Scores for Subtyping of Schizophrenia Schizophrenia Research and Treatment |
author_facet |
Jingchun Chen Travis Mize Jain-Shing Wu Elliot Hong Vishwajit Nimgaonkar Kenneth S. Kendler Daniel Allen Edwin Oh Alison Netski Xiangning Chen |
author_sort |
Jingchun Chen |
title |
Polygenic Risk Scores for Subtyping of Schizophrenia |
title_short |
Polygenic Risk Scores for Subtyping of Schizophrenia |
title_full |
Polygenic Risk Scores for Subtyping of Schizophrenia |
title_fullStr |
Polygenic Risk Scores for Subtyping of Schizophrenia |
title_full_unstemmed |
Polygenic Risk Scores for Subtyping of Schizophrenia |
title_sort |
polygenic risk scores for subtyping of schizophrenia |
publisher |
Hindawi Limited |
series |
Schizophrenia Research and Treatment |
issn |
2090-2085 2090-2093 |
publishDate |
2020-01-01 |
description |
Schizophrenia is a complex disorder with many comorbid conditions. In this study, we used polygenic risk scores (PRSs) from schizophrenia and comorbid traits to explore consistent cluster structure in schizophrenia patients. With 10 comorbid traits, we found a stable 4-cluster structure in two datasets (MGS and SSCCS). When the same traits and parameters were applied for the patients in a clinical trial of antipsychotics, the CATIE study, a 5-cluster structure was observed. One of the 4 clusters found in the MGS and SSCCS was further split into two clusters in CATIE, while the other 3 clusters remained unchanged. For the 5 CATIE clusters, we evaluated their association with the changes of clinical symptoms, neurocognitive functions, and laboratory tests between the enrollment baseline and the end of Phase I trial. Class I was found responsive to treatment, with significant reduction for the total, positive, and negative symptoms (p=0.0001, 0.0099, and 0.0028, respectively), and improvement for cognitive functions (VIGILANCE, p=0.0099; PROCESSING SPEED, p=0.0006; WORKING MEMORY, p=0.0023; and REASONING, p=0.0015). Class II had modest reduction of positive symptoms (p=0.0492) and better PROCESSING SPEED (p=0.0071). Class IV had a specific reduction of negative symptoms (p=0.0111) and modest cognitive improvement for all tested domains. Interestingly, Class IV was also associated with decreased lymphocyte counts and increased neutrophil counts, an indication of ongoing inflammation or immune dysfunction. In contrast, Classes III and V showed no symptom reduction but a higher level of phosphorus. Overall, our results suggest that PRSs from schizophrenia and comorbid traits can be utilized to classify patients into subtypes with distinctive clinical features. This genetic susceptibility based subtyping may be useful to facilitate more effective treatment and outcome prediction. |
url |
http://dx.doi.org/10.1155/2020/1638403 |
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