Distinct effect of prenatal and postnatal brain expression across 20 brain disorders and anthropometric social traits: a systematic study of spatiotemporal modularity.
Brief Bioinform
; 22(6)2021 11 05.
Article
em En
| MEDLINE
| ID: mdl-34086851
ABSTRACT
Different spatiotemporal abnormalities have been implicated in different neuropsychiatric disorders and anthropometric social traits, yet an investigation in the temporal network modularity with brain tissue transcriptomics has been lacking. We developed a supervised network approach to investigate the genome-wide association study (GWAS) results in the spatial and temporal contexts and demonstrated it in 20 brain disorders and anthropometric social traits. BrainSpan transcriptome profiles were used to discover significant modules enriched with trait susceptibility genes in a developmental stage-stratified manner. We investigated whether, and in which developmental stages, GWAS-implicated genes are coordinately expressed in brain transcriptome. We identified significant network modules for each disorder and trait at different developmental stages, providing a systematic view of network modularity at specific developmental stages for a myriad of brain disorders and traits. Specifically, we observed a strong pattern of the fetal origin for most psychiatric disorders and traits [such as schizophrenia (SCZ), bipolar disorder, obsessive-compulsive disorder and neuroticism], whereas increased co-expression activities of genes were more strongly associated with neurological diseases [such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis] and anthropometric traits (such as college completion, education and subjective well-being) in postnatal brains. Further analyses revealed enriched cell types and functional features that were supported and corroborated prior knowledge in specific brain disorders, such as clathrin-mediated endocytosis in AD, myelin sheath in multiple sclerosis and regulation of synaptic plasticity in both college completion and education. Our study provides a landscape view of the spatiotemporal features in a myriad of brain-related disorders and traits.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Encefalopatias
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Biomarcadores
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Biologia Computacional
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Característica Quantitativa Herdável
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Perfilação da Expressão Gênica
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Transcriptoma
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article