engFelsky, DanielSanta-Maria, IsmaelCosacak, Mehmet IlyasFrench, LeonSchneider, Julie ABennett, David ADe Jager, Philip LKizil, CaghanTosto, GiuseppeThe Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms.info:eu-repo/classification/ddc/570HumansTranscriptomeAlzheimer Disease: geneticsCaribbean PeopleEthnicityBrainGenetic Predisposition to DiseasePolymorphism, Single NucleotideLDL-Receptor Related Proteins: geneticsMembrane Transport Proteins: geneticsAlzheimer's diseaseBrain gene expressionBulk tissueCaribbean-HispanicSingle cellSORL1 protein, humanLDL-Receptor Related ProteinsMembrane Transport ProteinsIdentifying ancestry-specific molecular profiles of late-onset Alzheimer's Disease (LOAD) in brain tissue is crucial to understand novel mechanisms and develop effective interventions in non-European, high-risk populations. We performed gene differential expression (DE) and consensus network-based analyses in RNA-sequencing data of postmortem brain tissue from 39 Caribbean Hispanics (CH). To identify ancestry-concordant and -discordant expression profiles, we compared our results to those from two independent non-Hispanic White (NHW) samples (n = 731). In CH, we identified 2802 significant DE genes, including several LOAD known-loci. DE effects were highly concordant across ethnicities, with 373 genes transcriptome-wide significant in all three cohorts. Cross-ancestry meta-analysis found NPNT to be the top DE gene. We replicated over 82% of meta-analyses genome-wide signals in single-nucleus RNA-seq data (including NPNT and LOAD known-genes SORL1, FBXL7, CLU, ABCA7). Increasing representation in genetic studies will allow for deeper understanding of ancestry-specific mechanisms and improving precision treatment options in understudied groups.Neurobiology of disease 176, 105938 (2023). doi:10.1016/j.nbd.2022.105938info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionElsevier2023info:eu-repo/semantics/openAccessDEhttps://pub.dzne.de/record/169129https://pub.dzne.de/search?p=id:%22DZNE-2023-00008%22Researchersinfo:eu-repo/semantics/altIdentifier/pmid/pmid:36462719info:eu-repo/semantics/altIdentifier/issn/0969-9961info:eu-repo/semantics/altIdentifier/doi/10.1016/j.nbd.2022.105938info:eu-repo/semantics/altIdentifier/issn/1095-953X