Genome wide association study and next generation sequencing: A glimmer of light toward new possible horizons in frontotemporal dementia research: Frontiers in Neuroscience

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Frontotemporal Dementia (FTD) is a focal neurodegenerative disease, with a strong genetic background, that causes early onset dementia. The present knowledge about the risk loci and causative mutations of FTD mainly derives from genetic linkage analysis, studies of candidate genes, Genome-Wide Association Studies (GWAS) and Next-Generation Sequencing (NGS) applications. In this review, we report recent insights into the genetics of FTD, and, specifically, the results achieved thanks to GWAS and NGS approaches. Linkage studies of large FTD pedigrees have prompted the identification of causal mutations in different genes: mutations in C9orf72, MAPT, and GRN genes explain the large majority of cases with a high family history of the disease. In cases with a less clear inheritance, GWAS and NGS have contributed to further understand the genetic picture of FTD. GWAS identified several common genetic variants with a modest risk effect. Of interest, many of these variants are in genes belonging to the endo-lysosomal pathway, the immune response and neuronal survival. On the opposite, the NGS approach allowed the identification of rare variants with a strong risk effect. These variants were identified in known FTD-associated genes and again in genes involved in the endo-lysosomal pathway and in the immune response. Interestingly, both approaches demonstrated that several genes are associated to multiple neurodegenerative disorders including FTD. Thanks to these complementary approaches, the genetic picture of FTD is becoming more clear and novel key molecular processes are emerging. This will foster opportunities to move toward prevention and therapy for this incurable disease. Copyright © 2019 Ciani, Benussi, Bonvicini and Ghidoni. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Original languageEnglish
Article number506
JournalFront. Neurosci.
Issue numberMAY
Publication statusPublished - 2019


  • Frontotemporal dementia
  • Genetic common variants
  • Genetic mutations
  • Genetic rare variants
  • Genome wide association study
  • Next generation sequencing
  • TAR DNA binding protein
  • Article
  • frontotemporal dementia
  • gene
  • gene locus
  • gene mutation
  • gene rearrangement
  • genetic association
  • genetic variability
  • GRN gene
  • human
  • immune response
  • MAPT gene
  • next generation sequencing
  • phenotype
  • sequence homology
  • signal transduction
  • ubiquitination
  • whole genome sequencing


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