A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia

Raffaele Ferrari, Mario Grassi, Erika Salvi, Barbara Borroni, Fernando Palluzzi, Daniele Pepe, Francesca D'Avila, Alessandro Padovani, Silvana Archetti, Innocenzo Rainero, Elisa Rubino, Lorenzo Pinessi, Luisa Benussi, Giuliano Binetti, Roberta Ghidoni, Daniela Galimberti, Elio Scarpini, Maria Serpente, Giacomina Rossi, Giorgio GiacconeFabrizio Tagliavini, Benedetta Nacmias, Irene Piaceri, Silvia Bagnoli, Amalia C. Bruni, Raffaele G. Maletta, Livia Bernardi, Alfredo Postiglione, Graziella Milan, Massimo Franceschi, Annibale A. Puca, Valeria Novelli, Cristina Barlassina, Nicola Glorioso, Paolo Manunta, Andrew Singleton, Daniele Cusi, John Hardy, Parastoo Momeni

Research output: Contribution to journalArticlepeer-review


Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer's disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel single nucleotide polymorphisms (SNPs)-to-genes approach and functional annotation analysis. We identified 2 novel potential loci for FTD. Suggestive SNPs reached p-values ~10-7 and odds ratio > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation, and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-genome-wide association study. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis.

Original languageEnglish
Pages (from-to)2904.e13-2904.e26
JournalNeurobiology of Aging
Issue number10
Publication statusPublished - Oct 1 2015


  • Association study
  • Case-control
  • Frontotemporal dementia
  • Functional annotation
  • Genetic risk factors
  • Population

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology


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