Data di Pubblicazione:
2017
Citazione:
Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia / R. Ferrari, M. Grassi, F. Graziano, F. Palluzzi, S. Archetti, E. Bonomi, A.C. Bruni, R.G. Maletta, L. Bernardi, C. Cupidi, R. Colao, I. Rainero, E. Rubino, L. Pinessi, D. Galimberti, E. Scarpini, M. Serpente, B. Nacmias, I. Piaceri, S. Bagnoli, G. Rossi, G. Giaccone, F. Tagliavini, L. Benussi, G. Binetti, R. Ghidoni, A. Singleton, J. Hardy, P. Momeni, A. Padovani, B. Borroni. - In: JOURNAL OF ALZHEIMER'S DISEASE. - ISSN 1387-2877. - 56:4(2017), pp. 1271-1278. [10.3233/JAD-160949]
Abstract:
In frontotemporal dementia (FTD), age at disease onset (AAO) is unpredictable in both early and late-onset cases; AAO variability is found even in autosomal dominant FTD. The present study was aimed at identifying genetic modifiers modulating AAO in a large cohort of Italian FTD patients. We conducted an association analysis on 411 FTD patients, belonging to 7 Italian Centers, and for whom AAO was available. Population structure was evaluated by principal component analysis to infer continuous axes of genetic variation, and single linear regression models were applied. A genetic score (GS) was calculated on the basis of suggestive single nucleotide polymorphisms (SNPs) found by association analyses. GS showed genome-wide significant slope decrease by -3.86 (95 CI: -4.64 to -3.07, p<2Ã10-16) per standard deviation of the GS for 6 SNPs mapping to genes involved in neuronal development and signaling, axonal myelinization, and glutamatergic/GABA neurotransmission. An increase of the GS was associated with a decrease of the AAO. Our data indicate that there is indeed a genetic component that underpins and modulates up to 14.5 of variability of AAO in Italian FTD. Future studies on genetic modifiers in FTD are warranted.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
age at onset; frontotemporal dementia; GWAS; polymorphism; clinical psychology; geriatrics and gerontology; psychiatry and mental health
Elenco autori:
R. Ferrari, M. Grassi, F. Graziano, F. Palluzzi, S. Archetti, E. Bonomi, A.C. Bruni, R.G. Maletta, L. Bernardi, C. Cupidi, R. Colao, I. Rainero, E. Rubino, L. Pinessi, D. Galimberti, E. Scarpini, M. Serpente, B. Nacmias, I. Piaceri, S. Bagnoli, G. Rossi, G. Giaccone, F. Tagliavini, L. Benussi, G. Binetti, R. Ghidoni, A. Singleton, J. Hardy, P. Momeni, A. Padovani, B. Borroni
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