Transcriptome-wide association analysis of brain structures yields insights into pleiotropy with complex neuropsychiatric traits.
Nat Commun
; 12(1): 2878, 2021 05 17.
Article
em En
| MEDLINE
| ID: mdl-34001886
ABSTRACT
Structural variations of the human brain are heritable and highly polygenic traits, with hundreds of associated genes identified in recent genome-wide association studies (GWAS). Transcriptome-wide association studies (TWAS) can both prioritize these GWAS findings and also identify additional gene-trait associations. Here we perform cross-tissue TWAS analysis of 211 structural neuroimaging and discover 278 associated genes exceeding Bonferroni significance threshold of 1.04 × 10-8. The TWAS-significant genes for brain structures have been linked to a wide range of complex traits in different domains. Through TWAS gene-based polygenic risk scores (PRS) prediction, we find that TWAS PRS gains substantial power in association analysis compared to conventional variant-based GWAS PRS, and up to 6.97% of phenotypic variance (p-value = 7.56 × 10-31) can be explained in independent testing data sets. In conclusion, our study illustrates that TWAS can be a powerful supplement to traditional GWAS in imaging genetics studies for gene discovery-validation, genetic co-architecture analysis, and polygenic risk prediction.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Herança Multifatorial
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Perfilação da Expressão Gênica
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Estudo de Associação Genômica Ampla
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Pleiotropia Genética
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article