| Literature DB >> 26303663 |
G Nicolas1,2,3, C Charbonnier2,3, D Wallon2,3,4, O Quenez2,3, C Bellenguez5,6,7, B Grenier-Boley5,6,7, S Rousseau3, A-C Richard3, A Rovelet-Lecrux2, K Le Guennec2, D Bacq8, J-G Garnier8, R Olaso8, A Boland8, V Meyer8, J-F Deleuze8,9, P Amouyel5,6,7, H M Munter10, G Bourque10, M Lathrop10, T Frebourg1,2, R Redon11,12, L Letenneur13, J-F Dartigues13, E Génin14, J-C Lambert5,6,7, D Hannequin1,2,3,4, D Campion2,3,15.
Abstract
The SORL1 protein plays a protective role against the secretion of the amyloid β peptide, a key event in the pathogeny of Alzheimer's disease. We assessed the impact of SORL1 rare variants in early-onset Alzheimer's disease (EOAD) in a case-control setting. We conducted a whole exome analysis among 484 French EOAD patients and 498 ethnically matched controls. After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of disruptive and predicted damaging missense SORL1 variants in cases (odds radio (OR)=5.03, 95% confidence interval (CI)=(2.02-14.99), P=7.49.10(-5)). This enrichment was even stronger when restricting the analysis to the 205 cases with a positive family history (OR=8.86, 95% CI=(3.35-27.31), P=3.82.10(-7)). We conclude that predicted damaging rare SORL1 variants are a strong risk factor for EOAD and that the association signal is mainly driven by cases with positive family history.Entities:
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Year: 2015 PMID： 26303663 DOI： 10.1038/mp.2015.121
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 15.992