Abstract
Working memory deficit is the core neurocognitive disorder in schizophrenia patients. To identify the factors underlying working memory deficit in schizophrenia patients and to explore the implication of possible genes in the working memory using genome-wide association study (GWAS) of schizophrenia, computerized delay-matching-to-sample (DMS) and whole genome genotyping data were obtained from 100 first-episode, treatment-naïve patients with schizophrenia and 140 healthy controls from the Mental Health Centre of the West China Hospital, Sichuan University. A composite score, delay-matching-to-sample total correct numbers (DMS-TC), was found to be significantly different between the patients and control. On associating quantitative DMS-TC with interactive variables of groups × genotype, one SNP (rs1411832), located downstream of YWHAZP5 in chromosome 10, was found to be associated with the working memory deficit in schizophrenia patients with lowest p-value (p = 2.02 × 10−7). ConsensusPathDB identified that genes with SNPs for which p values below the threshold of 5 × 10−5 were significantly enriched in GO:0007155 (cell adhesion, p < 0.001). This study indicates that working memory, as an endophenotype of schizophrenia, could improve the efficacy of GWAS in schizophrenia. However, further study is required to replicate the results from our study.
Highlights
Schizophrenia is a psychiatric disorder that affects about 1% of the world population [1].Both win and adoption studies have shown that genetic factors play an important role in the pathogenesis of schizophrenia [2]
It was observed that delay-matching-to-sample total correct numbers (DMS-TC) score can be used for quantitative traits (QTs) in subsequent analysis
The current study is the first genome-wide association study (GWAS) utilizing one of the composite scores of the working memory task paradigm as QT to map common variants associated with schizophrenia
Summary
Schizophrenia is a psychiatric disorder that affects about 1% of the world population [1].Both win and adoption studies have shown that genetic factors play an important role in the pathogenesis of schizophrenia (heritability close to 0.8) [2]. The results from a GWA study with the largest sample size so far, identified 108 variants that are associated with schizophrenia. Some variants, such as ones in ZNF804A and variants in major histocompatibity complex (MHC), have been reported to be replicated, many SNPs were found to be non-overlapping in this study [7]. The inconsistency was attributed to factors such as population stratification, sample size, and clinical heterogeneity, with clinical heterogeneity being the most difficult confounding factor in case-control GWASs. Unlike other complex disorders, diagnosis of schizophrenia lacks reliable biomarkers and animal models. Various researchers used quantitative traits (QTs) as endophenotype or intermediate phenotype in order to enhance the efficacy of the GWAS in schizophrenia [8,9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
