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A Genome-Wide Screening and SNPs-to-Genes Approach to Identify Novel Genetic Risk Factors Associated with Frontotemporal Dementia

Ferrari, R; Grassi, M; Salvi, E; Borroni, B; Palluzzi, F; Pepe, D; D’Avila, F; ... Momeni, P; + view all (2015) A Genome-Wide Screening and SNPs-to-Genes Approach to Identify Novel Genetic Risk Factors Associated with Frontotemporal Dementia. Neurobiology of Aging , 36 (10) 2904 e.13-2904 e.26. 10.1016/j.neurobiolaging.2015.06.005. Green open access

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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 SNPs-to-genes approach and functional annotation analysis. We identified two novel potential loci for FTD. Suggestive SNPs reached p-values ~10-7 and OR > 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-GWAS. 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.

Type: Article
Title: A Genome-Wide Screening and SNPs-to-Genes Approach to Identify Novel Genetic Risk Factors Associated with Frontotemporal Dementia
Location: US
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neurobiolaging.2015.06.005
Publisher version: http://dx.doi.org/10.1016/j.neurobiolaging.2015.06...
Language: English
Additional information: Copyright © 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). http://dx.doi.org/10.1016/j.neurobiolaging.2015.06.005
Keywords: Frontotemporal dementia, association study, case-control, genetic risk factors, functional annotation, population.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/1469338
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