Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
| Autor: | Jia-Bei Chen, 陳佳蓓 |
|---|---|
| Rok vydání: | 2019 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 107 Background Despite a few genetic variants overlap between neurocognitive deficits and schizophrenia (SZ) revealed by genome-wide association studies (GWAS), the genetic architecture influencing patients’ neurocognitive performance remains unclear. This study aimed to (1) examine whether the neurocognitive performance in SZ patients could be explained by the polygenic risk score (PRS) derived from schizophrenia versus that derived from other neuropsychiatric disorders or neurocognitive traits; (2) to examine the magnitude of the association of the PRS with the neurocognitive performance in schizophrenia patients from different familial loadings; and (3) to compare the PRS among three subgroups of schizophrenia patients classified by their magnitude of impairment in sustained attention. Methods Participants were 1649 sporadic cases and 3298 parents without SZ in simplex families from Schizophrenia Trio Genomics Research in Taiwan. For multiplex families with at least two SZ siblings, there were 581 co-affected probands and 479 parents without SZ from Taiwan Schizophrenia Linkage Study. All were genotyped using PsychChip and only patients underwent Continuous Performance Test (CPT) and Wisconsin Card Sorting Test (WCST). Patients was categorized into three groups based on their magnitude of impairment in sustained attention to compare their PRS. Confirmatory factor analysis of a four-latent model structure was performed to capture patients’ performance on CPT and WCST. Meta-analyses GWAS data of SZ, bipolar disorder (BD), Alzheimer''s disease (AD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), educational attainment (EA), and general cognitive ability (GCA) were used to derive corresponding PRS. Results SZ patients in multiplex families had worse scores than simplex ones on most CPT and WCST indices. Among the seven PRS, the phenotype of schizophrenia could be predicted by SZ-PRS, BD-PRS, ASD-PRS, EA-PRS, and GCA-PRS in simplex families and by SZ-PRS in multiplex families. Only EA-PRS and GCA-PRS were significantly associated with higher WCST2 factors among patients with schizophrenia in simplex families. Furthermore, no impairment group in simplex families had the highest GCA-PRS and SZ-PRS. Conclusions The neurocognitive performance of schizophrenia patients was best explained by the general cognitive abilities PRS derived from healthy individuals rather than the schizophrenia and other neuropsychiatric disorders PRS derived from patients with neuropsychiatric disorders. Neurocognitive deficits in schizophrenia patients may involve modifier genes. Other genetic architecture underlying schizophrenia’s cognitive impairment warrants further investigation. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|