Ferrari, R;
Grassi, M;
Graziano, F;
Palluzzi, F;
Archetti, S;
Bonomi, E;
Bruni, AC;
... Borroni, B; + view all
(2017)
Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia.
Journal of Alzheimer's Disease
, 56
(4)
pp. 1271-1278.
10.3233/JAD-160949.
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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.
| Type: | Article |
|---|---|
| Title: | Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3233/JAD-160949 |
| Publisher version: | http://dx.doi.org/10.3233/JAD-160949 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, Age at onset, frontotemporal dementia, GWAS, polymorphism, Genome-Wide Association, Autism Spectrum Disorder, Alzheimer-Disease, Mutation Carriers, Ftld, Expression, Identification, Polymorphism, Individuals, Families |
| 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-pp.ucl.ac.uk/id/eprint/10048211 |
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