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@ARTICLE{Felsky:169129,
      author       = {Felsky, Daniel and Santa-Maria, Ismael and Cosacak, Mehmet
                      Ilyas and French, Leon and Schneider, Julie A and Bennett,
                      David A and De Jager, Philip L and Kizil, Caghan and Tosto,
                      Giuseppe},
      title        = {{T}he {C}aribbean-{H}ispanic {A}lzheimer's disease brain
                      transcriptome reveals ancestry-specific disease mechanisms.},
      journal      = {Neurobiology of disease},
      volume       = {176},
      issn         = {0969-9961},
      address      = {[Amsterdam]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2023-00008},
      pages        = {105938},
      year         = {2023},
      abstract     = {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 $82\%$ 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.},
      keywords     = {Humans / Transcriptome / Alzheimer Disease: genetics /
                      Caribbean People / Ethnicity / Brain / Genetic
                      Predisposition to Disease / Polymorphism, Single Nucleotide
                      / LDL-Receptor Related Proteins: genetics / Membrane
                      Transport Proteins: genetics / Alzheimer's disease (Other) /
                      Brain gene expression (Other) / Bulk tissue (Other) /
                      Caribbean-Hispanic (Other) / Single cell (Other) / SORL1
                      protein, human (NLM Chemicals) / LDL-Receptor Related
                      Proteins (NLM Chemicals) / Membrane Transport Proteins (NLM
                      Chemicals)},
      cin          = {AG Kizil},
      ddc          = {570},
      cid          = {I:(DE-2719)1710007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10039465},
      pubmed       = {pmid:36462719},
      doi          = {10.1016/j.nbd.2022.105938},
      url          = {https://pub.dzne.de/record/169129},
}