Transcriptome-wide association analysis of brain structures yields insights into pleiotropy with complex neuropsychiatric traits.

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

SUBMITTER: Zhao B 

PROVIDER: S-EPMC8128893 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature