SORL1 rare variants: a major risk factor for familial early-onset Alzheimer%26apos;s disease

作者：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; Genin E; Lambert J C; Hannequin D; Campion D

来源：Molecular Psychiatry, 2016, 21(6): 831-836.

DOI：10.1038/mp.2015.121

The SORL1 protein plays a protective role against the secretion of the amyloid beta 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.

• 出版日期2016-6
• 单位中国地震局