دورية أكاديمية
أعرض في EDS

Rare Copy Number Variants Are Associated With Poorer Cognition in Schizophrenia.

التفاصيل البيبلوغرافية
العنوان: Rare Copy Number Variants Are Associated With Poorer Cognition in Schizophrenia.
المؤلفون: Hubbard L; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Rees E; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Morris DW; CogGene Group, Centre for Neuroimaging, Cognition & Genomics, Discipline of Biochemistry and School of Psychology, Neuroimaging and Cognitive Genomics Centre, National University of Ireland, Galway, Ireland., Lynham AJ; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Richards AL; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Pardiñas AF; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Legge SE; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Harold D; School of Biotechnology, Dublin City University, Dublin, Ireland., Zammit S; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom., Corvin AC; Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine and Discipline of Psychiatry, Trinity College Dublin, Dublin, Ireland., Gill MG; Neuropsychiatric Genetics Research Group, Institute of Molecular Medicine and Discipline of Psychiatry, Trinity College Dublin, Dublin, Ireland., Hall J; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Holmans P; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., O'Donovan MC; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Owen MJ; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Donohoe G; CogGene Group, Centre for Neuroimaging, Cognition & Genomics, Discipline of Biochemistry and School of Psychology, Neuroimaging and Cognitive Genomics Centre, National University of Ireland, Galway, Ireland., Kirov G; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Pocklington A; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom., Walters JTR; MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom. Electronic address: WaltersJT@cf.ac.uk.
المصدر: Biological psychiatry [Biol Psychiatry] 2021 Jul 01; Vol. 90 (1), pp. 28-34. Date of Electronic Publication: 2020 Dec 19.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: United States NLM ID: 0213264 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2402 (Electronic) Linking ISSN: 00063223 NLM ISO Abbreviation: Biol Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: New York, NY : Elsevier
Original Publication: New York, Plenum Pub. Corp.
مواضيع طبية MeSH: Schizophrenia*/complications , Schizophrenia*/genetics, Adult ; Cognition ; DNA Copy Number Variations/genetics ; Genetic Predisposition to Disease ; Humans ; Intelligence Tests ; Phenotype
مستخلص: Background: Cognitive impairment in schizophrenia is a major contributor to poor outcomes, yet its causes are poorly understood. Some rare copy number variants (CNVs) are associated with schizophrenia risk and affect cognition in healthy populations, but their contribution to cognitive impairment in schizophrenia has not been investigated. We examined the effect of 12 schizophrenia CNVs on cognition in those with schizophrenia.
Methods: General cognitive ability was measured using the Measurement and Treatment Research to Improve Cognition in Schizophrenia composite z score in 875 patients with schizophrenia and in a replication sample of 519 patients with schizophrenia using Wechsler Adult Intelligence Scale Full Scale IQ. Using linear regression, we tested for association between cognition and schizophrenia CNV status, covarying for age and sex. In addition, we tested whether CNVs hitting genes in schizophrenia-enriched gene sets (loss-of-function intolerant and synaptic gene sets) were associated with cognitive impairment.
Results: A total of 23 schizophrenia CNV carriers were identified. Schizophrenia CNV carriers had lower general cognitive ability than nonschizophrenia CNV carriers in discovery (β = -0.66, 95% confidence interval [CI] = -1.31 to -0.01) and replication samples (β = -0.91, 95% CI = -1.71 to -0.11) and after meta-analysis (β = -0.76, 95% CI = -1.26 to -0.25, p = .003). CNVs hitting loss-of-function intolerant genes were associated with lower cognition (β = -0.15, 95% CI = -0.29 to -0.001, p = .048).
Conclusions: In those with schizophrenia, cognitive ability in schizophrenia CNV carriers is 0.5-1.0 standard deviations below non-CNV carriers, which may have implications for clinical assessment and management. We also demonstrate that rare CNVs hitting genes intolerant to loss-of-function variation lead to more severe cognitive impairment, above and beyond the effect of known schizophrenia CNVs.
(Copyright © 2021. Published by Elsevier Inc.)
التعليقات: Comment in: Biol Psychiatry. 2021 Jul 1;90(1):4-5. (PMID: 34140119)
معلومات مُعتمدة: MC_PC_17212 United Kingdom MRC_ Medical Research Council; MR/L010305/1 United Kingdom MRC_ Medical Research Council; MR/P005748/1 United Kingdom MRC_ Medical Research Council; G0800509 United Kingdom MRC_ Medical Research Council; MR/L011794/1 United Kingdom MRC_ Medical Research Council; 085475/B/08/Z United Kingdom WT_ Wellcome Trust; 085475/Z/08/Z United Kingdom WT_ Wellcome Trust; 072894/Z/03/Z United Kingdom WT_ Wellcome Trust; 090532/Z/09/Z United Kingdom WT_ Wellcome Trust; 075491/Z/04/B United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: CNV; Cognition; Copy number variation; General cognitive ability; Schizophrenia; Schizophrenia CNV
تواريخ الأحداث: Date Created: 20210308 Date Completed: 20210628 Latest Revision: 20220531
رمز التحديث: 20231215
DOI: 10.1016/j.biopsych.2020.11.025
PMID: 33678419
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-2402
DOI:10.1016/j.biopsych.2020.11.025