TY  - JOUR
AU  - Felsky, Daniel
AU  - Santa-Maria, Ismael
AU  - Cosacak, Mehmet Ilyas
AU  - French, Leon
AU  - Schneider, Julie A
AU  - Bennett, David A
AU  - De Jager, Philip L
AU  - Kizil, Caghan
AU  - Tosto, Giuseppe
TI  - The Caribbean-Hispanic Alzheimer's disease brain transcriptome reveals ancestry-specific disease mechanisms.
JO  - Neurobiology of disease
VL  - 176
SN  - 0969-9961
CY  - [Amsterdam]
PB  - Elsevier
M1  - DZNE-2023-00008
SP  - 105938
PY  - 2023
AB  - Identifying 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
KW  - Humans
KW  - Transcriptome
KW  - Alzheimer Disease: genetics
KW  - Caribbean People
KW  - Ethnicity
KW  - Brain
KW  - Genetic Predisposition to Disease
KW  - Polymorphism, Single Nucleotide
KW  - LDL-Receptor Related Proteins: genetics
KW  - Membrane Transport Proteins: genetics
KW  - Alzheimer's disease (Other)
KW  - Brain gene expression (Other)
KW  - Bulk tissue (Other)
KW  - Caribbean-Hispanic (Other)
KW  - Single cell (Other)
KW  - SORL1 protein, human (NLM Chemicals)
KW  - LDL-Receptor Related Proteins (NLM Chemicals)
KW  - Membrane Transport Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC10039465
C6  - pmid:36462719
DO  - DOI:10.1016/j.nbd.2022.105938
UR  - https://pub.dzne.de/record/169129
ER  -