SORL1 rare variants: a major risk factor for familial early-onset Alzheimer’s disease - Archive ouverte HAL Access content directly
Journal Articles Molecular Psychiatry Year : 2016

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

, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , (1) , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
1
Gaël Nicolas
C Charbonnier
  • Function : Author
David Wallon
  • Function : Author
O Quenez
  • Function : Author
C Bellenguez
  • Function : Author
B Grenier-Boley
  • Function : Author
S Rousseau
  • Function : Author
A-C Richard
  • Function : Author
A Rovelet-Lecrux
  • Function : Author
K Le Guennec
  • Function : Author
D Bacq
  • Function : Author
J-G Garnier
  • Function : Author
R Olaso
  • Function : Author
A Boland
  • Function : Author
V Meyer
  • Function : Author
J-F Deleuze
  • Function : Author
P Amouyel
H Munter
  • Function : Author
G Bourque
  • Function : Author
M Lathrop
  • Function : Author
T Frebourg
  • Function : Author
R Redon
  • Function : Author
L Letenneur
  • Function : Author
J-F Dartigues
  • Function : Author
E Génin
  • Function : Author
J-C Lambert
  • Function : Author
Didier Hannequin
  • Function : Author
Dominique Campion
  • Function : Author
Olivier Martinaud
  • Function : Author
Olivier Godefroy
Frédérique Etcharry-Bouyx
  • Function : Author
  • PersonId : 992844
Valérie Chauviré
  • Function : Author
Ludivine Chamard
  • Function : Author
Eric Berger
  • Function : Author
Eloi Magnin
Jean-Francois Dartigues
  • Function : Author
Sophie Auriacombe
  • Function : Author
Vincent de La Sayette
  • Function : Author
Fausto Viader
  • Function : Author
Dominique Castan
  • Function : Author
Elsa Dionet
  • Function : Author
François Sellal
  • Function : Author
Olivier Rouaud
Christel Thauvin
  • Function : Author
Olivier Moreaud
  • Function : Author
Mathilde Sauvée
  • Function : Author
Adeline Rollin-Sillaire
  • Function : Author
Stéphanie Bombois
  • Function : Author
Marie-Anne Mackowiak
  • Function : Author
Vincent Deramecourt
  • Function : Author
Florence Pasquier
  • Function : Author
Maïté Formaglio
  • Function : Author
Hélène Mollion
  • Function : Author
Isabelle Roullet-Solignac
  • Function : Author
Alain Vighetto
  • Function : Author
Bernard Croisile
  • Function : Author
Mira Didic
Olivier Félician
  • Function : Author
Lejla Koric
  • Function : Author
Mathieu Ceccaldi
Audrey Gabelle
Cecilia Marelli
  • Function : Author
Jacques Touchon
  • Function : Author
Pierre Labauge
Thérèse Jonveaux
  • Function : Author
Martine Vercelletto
  • Function : Author
Claire Boutoleau-Bretonnière
  • Function : Author
Giovanni Castelnovo
  • Function : Author
David Renaud
  • Function : Author
Philippe Robert
Claire Paquet
  • Function : Author
Julien Dumurgier
Jacques Hugon
  • Function : Author
Agnès Michon
  • Function : Author
Isabelle Le Ber
  • Function : Author
Bruno Dubois
  • Function : Author
Charles Duyckaerts
  • Function : Author
Foucauld de Boisgueheneuc
  • Function : Author
Serge Belliard
  • Function : Author
Serge Bakchine
  • Function : Author
Marie-Odile Barrellon
  • Function : Author
Bernard Laurent
  • Function : Author
Frédéric Blanc
Christine Tranchant
  • Function : Author
Jérémie Pariente
  • Function : Author
Michèle Puel
  • Function : Author
Caroline Hommet
  • Function : Author
Karl Mondon
  • Function : Author

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.
Not file

Dates and versions

hal-03630222 , version 1 (04-04-2022)

Identifiers

Cite

Gaël Nicolas, C Charbonnier, David Wallon, O Quenez, C Bellenguez, et al.. SORL1 rare variants: a major risk factor for familial early-onset Alzheimer’s disease. Molecular Psychiatry, 2016, 21 (6), pp.831-836. ⟨10.1038/mp.2015.121⟩. ⟨hal-03630222⟩
26 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More