BACKGROUND: Genetic control of gene expression in asthma-related tissues is not well-characterized, particularly for African-ancestry populations, limiting advancement in our understanding of the increased prevalence and severity of asthma in those populations. OBJECTIVE: To create novel transcriptome prediction models for asthma tissues (nasal epithelium and CD4+ T cells) and apply them in transcriptome-wide association study (TWAS) to discover candidate asthma genes. METHODS: We developed and validated gene expression prediction databases for unstimulated CD4+ T cells (CD4+T) and nasal epithelium using an elastic net framework. Combining these with existing prediction databases (N=51), we performed TWAS of 9,284 individuals of African-ancestry to identify tissue-specific and cross-tissue candidate genes for asthma. For detailed Methods, please see the Supplemental Methods. RESULTS: Novel databases for CD4+T and nasal epithelial gene expression prediction contain 8,351 and 10,296 genes, respectively, including four asthma loci ( CONCLUSIONS: Expression of KEY MESSAGES: From the largest African-ancestry TWAS of asthma to date (N=9,284), we identified 17 candidate causal asthma genes, including: nasal epithelial expression of CAPSULE SUMMARY: We developed novel gene expression prediction databases (CD4+ T cells, nasal airway epithelium) representing diverse populations across the African diaspora and identified 17 candidate causal asthma genes from TWAS.