Published in

Springer Nature [academic journals on nature.com], Molecular Psychiatry, 6(21), p. 831-836, 2015

DOI: 10.1038/mp.2015.121

Links

Tools

Export citation

Search in Google Scholar

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

Journal article published in 2015 by David Wallon, Vincent de la Sayette, G. Nicolas, C. Charbonnier, D. Wallon, O. Quenez, C. Bellenguez, B. Grenier-Boley, S. Rousseau, A.-C. Richard, A. Rovelet-Lecrux, K. Le Guennec, D. Bacq, J.-G. Garnier, R. Olaso and other authors.
This paper is available in a repository.
This paper is available in a repository.

Full text: Download

Green circle
Preprint: archiving allowed
Orange circle
Postprint: archiving restricted
Red circle
Published version: archiving forbidden
Data provided by SHERPA/RoMEO

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.Molecular Psychiatry advance online publication, 25 August 2015; doi:10.1038/mp.2015.121.