ABCA7 rare variants and Alzheimer disease risk

Kilan Le Guennec (1) , Gaël Nicolas (1, 2) , Olivier Quenez (1, 2) , Camille Charbonnier (1) , David Wallon (3) , Céline Bellenguez (4) , Benjamin Grenier-Boley (4) , Stéphane Rousseau (1) , Anne-Claire Richard (5) , Anne Rovelet-Lecrux (1) , Delphine Bacq , Jean-Guillaume Garnier (6) , Robert Olaso (6) , Anne Boland (6) , Vincent Meyer (7) , Jean-François Deleuze (8) , Philippe Amouyel (9) , Hans Markus Munter (10) , Guillaume Bourque (10) , Mark Lathrop , Thierry Frebourg , Richard Redon (11) , Luc Letenneur , Jean-François Dartigues , Florence Pasquier , Adeline Rollin-Sillaire , Emmanuelle Génin (12) , Jean-Charles Lambert , Didier Hannequin , Dominique Campion , Olivier Godefroy (13, 14)

1 GMFC - Génétique du cancer et des maladies neuropsychiatriques
2 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
3 Service de neurologie [Rouen]
4 Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations
5 IRIB - Institute for Research and Innovation in Biomedicine
6 CNG - Centre National de Génotypage
7 Lafarge LCR Lyon - Lafarge Centre de Recherche [Lyon]
8 Centre de Ressources Biologiques [Evry]
9 RID-AGE - Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167
10 McGill University and Genome Quebec Innovation Centre
11 ITX - ITX - unité de recherche de l'institut du thorax
12 GGB - Génétique, génomique fonctionnelle et biotechnologies (UMR 1078)
13 CHU Amiens-Picardie
14 LNFP - Laboratoire de Neurosciences Fonctionnelles et Pathologies - UR UPJV 4559

OBJECTIVE: To study the association between ABCA7 rare coding variants and Alzheimer disease (AD) in a case-control setting. METHODS: We conducted a whole exome analysis among 484 French patients with early-onset AD and 590 ethnically matched controls. RESULTS: After collapsing rare variants (minor allele frequency ≤1%), we detected an enrichment of ABCA7 loss of function (LOF) and predicted damaging missense variants in cases (odds ratio [OR] 3.40, 95% confidence interval [CI] 1.68-7.35, p = 0.0002). Performing a meta-analysis with previously published data, we found that in a combined sample of 1,256 patients and 1,347 controls from France and Belgium, the OR was 2.81 (95% CI 1.89-4.20, p = 3.60 × 10(-7)). CONCLUSIONS: These results confirm that ABCA7 LOF variants are enriched in patients with AD and extend this finding to predicted damaging missense variants.

Domaines: Sciences du Vivant [q-bio]

Kilan Le Guennec, Gaël Nicolas, Olivier Quenez, Camille Charbonnier, David Wallon, et al.. ABCA7 rare variants and Alzheimer disease risk. Neurology, 2016, Equipe 4, 86 (23), pp.2134--2137. ⟨10.1212/WNL.0000000000002627⟩. ⟨hal-01831744⟩