Details

Autor(en) / Beteiligte

• Nicolas, G
• Charbonnier, C
• Wallon, D
• Quenez, O
• Bellenguez, C
• Grenier-Boley, B
• Rousseau, S
• Richard, A-C
• Rovelet-Lecrux, A
• Le Guennec, K
• Bacq, D
• Garnier, J-G
• Olaso, R
• Boland, A
• Meyer, V
• Deleuze, J-F
• Amouyel, P
• Munter, H M
• Bourque, G
• Lathrop, M
• Frebourg, T
• Redon, R
• Letenneur, L
• Dartigues, J-F
• Génin, E
• Lambert, J-C
• Hannequin, D
• Campion, D

Titel

SORL1 rare variants: a major risk factor for familial early-onset Alzheimer's disease

Ist Teil von

• Molecular psychiatry, 2016-06, Vol.21 (6), p.831-836

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.