RESUMEN
Identification of therapeutic targets from genome-wide association studies (GWAS) requires insights into downstream functional consequences. We harmonized 8,613 RNA-sequencing samples from 14 brain datasets to create the MetaBrain resource and performed cis- and trans-expression quantitative trait locus (eQTL) meta-analyses in multiple brain region- and ancestry-specific datasets (n ≤ 2,759). Many of the 16,169 cortex cis-eQTLs were tissue-dependent when compared with blood cis-eQTLs. We inferred brain cell types for 3,549 cis-eQTLs by interaction analysis. We prioritized 186 cis-eQTLs for 31 brain-related traits using Mendelian randomization and co-localization including 40 cis-eQTLs with an inferred cell type, such as a neuron-specific cis-eQTL (CYP24A1) for multiple sclerosis. We further describe 737 trans-eQTLs for 526 unique variants and 108 unique genes. We used brain-specific gene-co-regulation networks to link GWAS loci and prioritize additional genes for five central nervous system diseases. This study represents a valuable resource for post-GWAS research on central nervous system diseases.
Asunto(s)
Encefalopatías , Sitios de Carácter Cuantitativo , Humanos , Sitios de Carácter Cuantitativo/genética , Estudio de Asociación del Genoma Completo , Redes Reguladoras de Genes/genética , Encéfalo , Fenotipo , Encefalopatías/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Potato taste defect (PTD) is a flavor defect in East African coffee associated with Antestiopsis orbitalis feeding and 3-isopropyl-2-methoxypyrazine (IPMP) in the coffee. To elucidate the manifestation of PTD, surface and interior volatile compounds of PTD and non-PTD green coffees were sampled by headspace solid phase microextraction and analyzed by gas chromatography mass spectrometry. Principal component analysis of the chromatographic data revealed a profile of surface volatiles distinguishing PTD from non-PTD coffees dominated by tridecane, dodecane, and tetradecane. While not detected in surface volatiles, IPMP was found in interior volatiles of PTD coffee. Desiccated antestia bugs were analyzed by GCMS, revealing that the three most prevalent volatiles were tridecane, dodecane, and tetradecane, as was found in the surface profile PTD coffee. Coffee having visible insect damage exhibited both a PTD surface volatile profile and IPMP in interior volatiles, supporting the hypothesis linking antestia bug feeding activity with PTD profile compounds on the surface and IPMP in the interior of the beans.
