Effects of Multiple Genetic Loci on Age at Onset in Frontotemporal Dementia.
J Alzheimers Dis
; 56(4): 1271-1278, 2017.
Article
em En
| MEDLINE
| ID: mdl-28128768
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, pâ<â2×10-16) 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Demência Frontotemporal
/
Loci Gênicos
Tipo de estudo:
Clinical_trials
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Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Humans
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Alzheimers Dis
Assunto da revista:
GERIATRIA
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NEUROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article