Integrative analysis of transcriptome-wide association study and mRNA expression profile identified risk genes for bipolar disorder

• Published in: Neuroscience letters 2024-09, Vol.839, p.137935, Article 137935
• Main Authors: Yang, Runxu, Wang, Rui, Zhao, Dongyan, Lian, Kun, Shang, Binli, Dong, Lei, Yang, Xuejuan, Dang, Xinglun, Sun, Duo, Cheng, Yuqi
• Format: Article
• Language: English
• Subjects: Bipolar disorder; Bipolar Disorder - genetics; Enrichment analysis; Female; Gene Expression Profiling - methods; Genetic Predisposition to Disease - genetics; Genome-Wide Association Study; Humans; Male; Pedigrees; Quantitative Trait Loci; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcriptome; Transcriptome-wide association study
• ISSN: 0304-3940; 1872-7972; 1872-7972
• DOI: 10.1016/j.neulet.2024.137935

Bipolar disorder (BD) is a debilitating neuropsychiatric disorder, which is associated with genetic variation through “vast but mixed” Genome-Wide Association Studies (GWAS). Transcriptome-Wide Association Study (TWAS) is more effective in explaining genetic factors that influence complex diseases and can help identifying risk genes more reliably. So, this study aims to identify potential BD risk genes in pedigrees with TWAS. We conducted a TWAS analysis with expression quantitative trait loci (eQTL) analysis on extended BD pedigrees, and the BD genome-wide association study (GWAS) summary data acquired from the Psychiatric Genomics Consortium (PGC). Furthermore, the BD-associated genes identified by TWAS were validated by mRNA expression profiles from the Gene Expression Omnibus (GEO) Datasets (GSE23848 and GSE46416). Functional enrichment and annotation analysis were implemented by RStudio (version 4.2.0). TWAS identified 362 genes with P value