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

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...

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Autores principales: Ferrari, Raffaele, Grassi, Mario, Salvi, Erika, Borroni, Barbara, Palluzzi, Fernando, Pepe, Daniele, D'Avila, Francesca, Padovani, Alessandro, Archetti, Silvana, Rainero, Innocenzo, Rubino, Elisa, Pinessi, Lorenzo, Benussi, Luisa, Binetti, Giuliano, Ghidoni, Roberta, Galimberti, Daniela, Scarpini, Elio, Serpente, Maria, Rossi, Giacomina, Giaccone, Giorgio, Tagliavini, Fabrizio, Nacmias, Benedetta, Piaceri, Irene, Bagnoli, Silvia, Bruni, Amalia C., Maletta, Raffaele G., Bernardi, Livia, Postiglione, Alfredo, Milan, Graziella, Franceschi, Massimo, Puca, Annibale A., Novelli, Valeria, Barlassina, Cristina, Glorioso, Nicola, Manunta, Paolo, Singleton, Andrew, Cusi, Daniele, Hardy, John, Momeni, Parastoo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706156/
https://www.ncbi.nlm.nih.gov/pubmed/26154020
http://dx.doi.org/10.1016/j.neurobiolaging.2015.06.005
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author Ferrari, Raffaele
Grassi, Mario
Salvi, Erika
Borroni, Barbara
Palluzzi, Fernando
Pepe, Daniele
D'Avila, Francesca
Padovani, Alessandro
Archetti, Silvana
Rainero, Innocenzo
Rubino, Elisa
Pinessi, Lorenzo
Benussi, Luisa
Binetti, Giuliano
Ghidoni, Roberta
Galimberti, Daniela
Scarpini, Elio
Serpente, Maria
Rossi, Giacomina
Giaccone, Giorgio
Tagliavini, Fabrizio
Nacmias, Benedetta
Piaceri, Irene
Bagnoli, Silvia
Bruni, Amalia C.
Maletta, Raffaele G.
Bernardi, Livia
Postiglione, Alfredo
Milan, Graziella
Franceschi, Massimo
Puca, Annibale A.
Novelli, Valeria
Barlassina, Cristina
Glorioso, Nicola
Manunta, Paolo
Singleton, Andrew
Cusi, Daniele
Hardy, John
Momeni, Parastoo
author_facet Ferrari, Raffaele
Grassi, Mario
Salvi, Erika
Borroni, Barbara
Palluzzi, Fernando
Pepe, Daniele
D'Avila, Francesca
Padovani, Alessandro
Archetti, Silvana
Rainero, Innocenzo
Rubino, Elisa
Pinessi, Lorenzo
Benussi, Luisa
Binetti, Giuliano
Ghidoni, Roberta
Galimberti, Daniela
Scarpini, Elio
Serpente, Maria
Rossi, Giacomina
Giaccone, Giorgio
Tagliavini, Fabrizio
Nacmias, Benedetta
Piaceri, Irene
Bagnoli, Silvia
Bruni, Amalia C.
Maletta, Raffaele G.
Bernardi, Livia
Postiglione, Alfredo
Milan, Graziella
Franceschi, Massimo
Puca, Annibale A.
Novelli, Valeria
Barlassina, Cristina
Glorioso, Nicola
Manunta, Paolo
Singleton, Andrew
Cusi, Daniele
Hardy, John
Momeni, Parastoo
author_sort Ferrari, Raffaele
collection PubMed
description 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.
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spelling pubmed-47061562016-02-08 A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia Ferrari, Raffaele Grassi, Mario Salvi, Erika Borroni, Barbara Palluzzi, Fernando Pepe, Daniele D'Avila, Francesca Padovani, Alessandro Archetti, Silvana Rainero, Innocenzo Rubino, Elisa Pinessi, Lorenzo Benussi, Luisa Binetti, Giuliano Ghidoni, Roberta Galimberti, Daniela Scarpini, Elio Serpente, Maria Rossi, Giacomina Giaccone, Giorgio Tagliavini, Fabrizio Nacmias, Benedetta Piaceri, Irene Bagnoli, Silvia Bruni, Amalia C. Maletta, Raffaele G. Bernardi, Livia Postiglione, Alfredo Milan, Graziella Franceschi, Massimo Puca, Annibale A. Novelli, Valeria Barlassina, Cristina Glorioso, Nicola Manunta, Paolo Singleton, Andrew Cusi, Daniele Hardy, John Momeni, Parastoo Neurobiol Aging Genetic Report Abstract 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. Elsevier 2015-10 /pmc/articles/PMC4706156/ /pubmed/26154020 http://dx.doi.org/10.1016/j.neurobiolaging.2015.06.005 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Genetic Report Abstract
Ferrari, Raffaele
Grassi, Mario
Salvi, Erika
Borroni, Barbara
Palluzzi, Fernando
Pepe, Daniele
D'Avila, Francesca
Padovani, Alessandro
Archetti, Silvana
Rainero, Innocenzo
Rubino, Elisa
Pinessi, Lorenzo
Benussi, Luisa
Binetti, Giuliano
Ghidoni, Roberta
Galimberti, Daniela
Scarpini, Elio
Serpente, Maria
Rossi, Giacomina
Giaccone, Giorgio
Tagliavini, Fabrizio
Nacmias, Benedetta
Piaceri, Irene
Bagnoli, Silvia
Bruni, Amalia C.
Maletta, Raffaele G.
Bernardi, Livia
Postiglione, Alfredo
Milan, Graziella
Franceschi, Massimo
Puca, Annibale A.
Novelli, Valeria
Barlassina, Cristina
Glorioso, Nicola
Manunta, Paolo
Singleton, Andrew
Cusi, Daniele
Hardy, John
Momeni, Parastoo
A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia
title A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia
title_full A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia
title_fullStr A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia
title_full_unstemmed A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia
title_short A genome-wide screening and SNPs-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia
title_sort genome-wide screening and snps-to-genes approach to identify novel genetic risk factors associated with frontotemporal dementia
topic Genetic Report Abstract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4706156/
https://www.ncbi.nlm.nih.gov/pubmed/26154020
http://dx.doi.org/10.1016/j.neurobiolaging.2015.06.005
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