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Joint evaluation of serum C-Reactive Protein levels and polygenic risk scores as risk factors for schizophrenia.

ABSTRACT: Several studies have indicated infectious and immune-related abnormalities in schizophrenia (Scz), including elevated serum C-reactive protein (CRP) - a well-known proxy for infections/immune abnormalities. A portion of the genetic risk for Scz can be estimated using the polygenic risk score (PGRS). It is not known whether there is an interaction in the risks traceable to CRP and PGRS. Patients with Scz and individuals without psychosis were evaluated systematically using DSM IV criteria (N=794, N=446, respectively). To estimate risk for Scz attributable to CRP and PGRS, serum from these participants was assayed for CRP levels using enzyme linked immunosorbent assays. PGRS was estimated from common DNA polymorphisms associated with Scz from genome wide association studies. CRP level and PGRS were not significantly correlated. Using a generalized linear logistic model, case/control status was evaluated in relation to the following predictors: CRP, PGRS, and demographic variables. CRP and PGRS were individually associated with case status; CRP: odds ratio (OR) 1.27, 95% confidence intervals (95% CI) 1.12, 1.43; p = 0.0001; PGRS: OR 1.66, 95% CI 1.47, 1.89; p = 1.28 ×10-15. There were no significant interactions between PGRS and CRP for predicting Scz versus control status.

SUBMITTER: Nimgaonkar VL

PROVIDER: S-EPMC6941903 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Joint evaluation of serum C-Reactive Protein levels and polygenic risk scores as risk factors for schizophrenia.

Nimgaonkar Vishwajit L VL Dickerson Faith F Pouget Jennie G JG Chowdari Kodavali K O'Dushlaine Colm C Wood Joel J Klei Lambertus L Devlin Bernie B Yolken Robert R

Psychiatry research 20171221

Several studies have indicated infectious and immune-related abnormalities in schizophrenia (Scz), including elevated serum C-reactive protein (CRP) - a well-known proxy for infections/immune abnormalities. A portion of the genetic risk for Scz can be estimated using the polygenic risk score (PGRS). It is not known whether there is an interaction in the risks traceable to CRP and PGRS. Patients with Scz and individuals without psychosis were evaluated systematically using DSM IV criteria (N=794, ...[more]

PMID: 29306175

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Project description:Patients with schizophrenia display characteristic smoking-related behaviors and genetic correlations between smoking behaviors and schizophrenia have been identified in European individuals. However, the genetic etiology of the association remains to be clarified. The present study investigated transethnic genetic overlaps between European-based smoking behaviors and the risk of Japanese schizophrenia by conducting polygenic risk score (PRS) analyses. Large-scale European genome-wide association study (GWAS) datasets (n = 24,114-74,035) related to four smoking-related intermediate phenotypes [(i) smoking initiation, (ii) age at smoking initiation, (iii) smoking quantity, and (iv) smoking cessation] were utilized as discovery samples. PRSs derived from these discovery GWASs were calculated for 332 Japanese subjects [schizophrenia patients, their unaffected first-degree relatives (FRs), and healthy controls (HCs)] as a target sample. Based on GWASs of European smoking phenotypes, we investigated the effects of PRSs on smoking phenotypes and the risk of schizophrenia in the Japanese population. Of the four smoking-related behaviors, the PRSs for age at smoking initiation in Europeans significantly predicted the age at smoking initiation (R2 = 0.049, p = 0.026) and the PRSs for smoking cessation significantly predicted the smoking cessation (R2 = 0.092, p = 0.027) in Japanese ever-smokers. Furthermore, the PRSs related to age at smoking initiation in Europeans were higher in Japanese schizophrenia patients than in the HCs and those of the FRs were intermediate between those of patients with schizophrenia and those of the HCs (R2 = 0.015, p = 0.015). In our target subjects, patients with schizophrenia had a higher mean age at smoking initiation (p = 0.018) and rate of daily smoking initiation after age 20 years (p = 0.023) compared with the HCs. A total of 60.6% of the patients started to smoke before the onset of schizophrenia. These findings suggest that genetic factors affecting late smoking initiation are associated with the risk of schizophrenia.

Dataset Information

Joint evaluation of serum C-Reactive Protein levels and polygenic risk scores as risk factors for schizophrenia.

Publications

Joint evaluation of serum C-Reactive Protein levels and polygenic risk scores as risk factors for schizophrenia.

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