%0 Journal Article %J J Alzheimers Dis %D 2017 %T Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia. %A Ferrari, Raffaele %A Grassi, Mario %A Graziano, Francesca %A Palluzzi, Fernando %A Archetti, Silvana %A Bonomi, Elisa %A Bruni, Amalia C %A Maletta, Raffaele G %A Bernardi, Livia %A Cupidi, Chiara %A Colao, Rosanna %A Rainero, Innocenzo %A Rubino, Elisa %A Pinessi, Lorenzo %A Galimberti, Daniela %A Scarpini, Elio %A Serpente, Maria %A Nacmias, Benedetta %A Piaceri, Irene %A Bagnoli, Silvia %A Rossi, Giacomina %A Giaccone, Giorgio %A Tagliavini, Fabrizio %A Benussi, Luisa %A Binetti, Giuliano %A Ghidoni, Roberta %A Singleton, Andrew %A Hardy, John %A Momeni, Parastoo %A Padovani, Alessandro %A Borroni, Barbara %X

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.

%B J Alzheimers Dis %V 56 %P 1271-1278 %8 2017 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/28128768?dopt=Abstract %R 10.3233/JAD-160949