Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities

碩士 === 國立臺灣大學 === 流行病學與預防醫學研究所 === 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...

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Main Authors: Jia-Bei Chen, 陳佳蓓
Other Authors: Wei-J. Chen
Format: Others
Language:en_US
Published: 2019
Online Access:http://ndltd.ncl.edu.tw/handle/5w25na
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spelling ndltd-TW-107NTU055440172019-11-16T05:27:54Z http://ndltd.ncl.edu.tw/handle/5w25na Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities 不同家庭負載之思覺失調症病患的神經認知表現: 比較不同神經精神疾病或一般認知能力之多基因分數的預測 Jia-Bei Chen 陳佳蓓 碩士 國立臺灣大學 流行病學與預防醫學研究所 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. Wei-J. Chen 陳為堅 2019 學位論文 ; thesis 71 en_US
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description 碩士 === 國立臺灣大學 === 流行病學與預防醫學研究所 === 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.
author2 Wei-J. Chen
author_facet Wei-J. Chen
Jia-Bei Chen
陳佳蓓
author Jia-Bei Chen
陳佳蓓
spellingShingle Jia-Bei Chen
陳佳蓓
Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
author_sort Jia-Bei Chen
title Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
title_short Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
title_full Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
title_fullStr Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
title_full_unstemmed Neurocognitive performance in schizophrenia patients with different familial loadings: Comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
title_sort neurocognitive performance in schizophrenia patients with different familial loadings: comparing predictions using polygenic scores derived from different neuropsychiatric disorders or general cognitive abilities
publishDate 2019
url http://ndltd.ncl.edu.tw/handle/5w25na
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