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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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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. |
format | Online Article Text |
id | pubmed-4706156 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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