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Titles listRare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia
Titles listRare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia
Scientific Article
unige:116068 
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Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia |
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| Collaboration | With : Frisoni, Giovanni | |
| Published in | Neurobiology of Aging. 2018, vol. 66, p. 181.e3-181.e10 | |
| Abstract | We investigated the genetic role of sortilin (SORT1) in frontotemporal dementia (FTD). SORT1 is the neuronal receptor for granulin, encoded by the progranulin gene (GRN), a major causal gene for inherited FTD. In Belgian cohorts of 636 FTD patients and 1066 unaffected control individuals, we identified 5 patient-only nonsynonymous rare variants in SORT1. Rare variant burden analysis showed a significant increase in rare coding variants in patients compared to control individuals (p = 0.04), particularly in the β-propeller domain (p = 0.04), with 2 rare variants located in the predicted binding site for GRN (p = 0.001). We extended these observations by analyzing 3 independent patient/control cohorts sampled in Spain, Italy, and Portugal by partners of the European Early-Onset Dementia Consortium, together with 1155 FTD patients and 1161 control persons. An additional 7 patient-only nonsynonymous variants were observed in SORT1 in European patients. Meta-analysis of the rare nonsynonymous variants in the Belgian and European patient/control cohorts revealed a significant enrichment in FTD patients (p = 0.006), establishing SORT1 as a genetic risk factor for FTD. | |
| Keywords | Adaptor Proteins, Vesicular Transport/chemistry/genetics — Aged — Belgium — Binding Sites — Cohort Studies — Europe — Female — Genetic Association Studies — Genetic Variation/genetics — Humans — Intercellular Signaling Peptides and Proteins — Male — Middle Aged — Progranulins — Protein Binding — Protein Domains — Risk | |
| Identifiers | PMID: 29555433 | |
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| Research group | Troubles de mémoire et maladie d'Alzeimer (935) | |
| Citation (ISO format) | BELNEU CONSORTIUM, EU EOD CONSORTIUM. Rare nonsynonymous variants in SORT1 are associated with increased risk for frontotemporal dementia. In: Neurobiology of Aging, 2018, vol. 66, p. 181.e3-181.e10. https://archive-ouverte.unige.ch/unige:116068 |
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