Title | Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Ferrari, R, Grassi, M, Graziano, F, Palluzzi, F, Archetti, S, Bonomi, E, Bruni, AC, Maletta, RG, Bernardi, L, Cupidi, C, Colao, R, Rainero, I, Rubino, E, Pinessi, L, Galimberti, D, Scarpini, E, Serpente, M, Nacmias, B, Piaceri, I, Bagnoli, S, Rossi, G, Giaccone, G, Tagliavini, F, Benussi, L, Binetti, G, Ghidoni, R, Singleton, A, Hardy, J, Momeni, P, Padovani, A, Borroni, B |
Journal | J Alzheimers Dis |
Volume | 56 |
Issue | 4 |
Pagination | 1271-1278 |
Date Published | 2017 |
ISSN | 1875-8908 |
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 < 2×10-16) 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. |
DOI | 10.3233/JAD-160949 |
Alternate Journal | J. Alzheimers Dis. |
PubMed ID | 28128768 |
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