Meta-Analysis

. 2016 Jun 7;86(23):2134-7.

doi: 10.1212/WNL.0000000000002627. Epub 2016 Apr 1.

ABCA7 rare variants and Alzheimer disease risk

Kilan Le Guennec¹, Gaël Nicolas¹, Olivier Quenez¹, Camille Charbonnier¹, David Wallon¹, Céline Bellenguez¹, Benjamin Grenier-Boley¹, Stéphane Rousseau¹, Anne-Claire Richard¹, Anne Rovelet-Lecrux¹, Delphine Bacq¹, Jean-Guillaume Garnier¹, Robert Olaso¹, Anne Boland¹, Vincent Meyer¹, Jean-François Deleuze¹, Philippe Amouyel¹, Hans Markus Munter¹, Guillaume Bourque¹, Mark Lathrop¹, Thierry Frebourg¹, Richard Redon¹, Luc Letenneur¹, Jean-François Dartigues¹, Florence Pasquier¹, Adeline Rollin-Sillaire¹, Emmanuelle Génin¹, Jean-Charles Lambert¹, Didier Hannequin¹, Dominique Campion; CNR-MAJ collaborators

Collaborators, Affiliations

Collaborators

CNR-MAJ collaborators:
Didier Hannequin, Dominique Campion, David Wallon, Olivier Martinaud, Gaël Nicolas, Adeline Rollin-Sillaire, Stéphanie Bombois, Marie-Anne Mackowiak, Vincent Deramecourt, Florence Pasquier, Agnès Michon, Isabelle Le Ber, Bruno Dubois, Charles Duyckaerts, Olivier Godefroy, Frédérique Etcharry-Bouyx, Valérie Chauviré, Ludivine Chamard, Eric Berger, Eloi Magnin, Jean-Francois Dartigues, Sophie Auriacombe, François Tison, Cyril Goizet, Vincent de la Sayette, Fausto Viader, Dominique Castan, Elsa Dionet, Francois Sellal, Olivier Rouaud, Christel Thauvin, Olivier Moreaud, Mathilde Sauvée, Maïté Formaglio, Hélène Mollion, Isabelle Roullet-Solignac, Alain Vighetto, Bernard Croisile, Mira Didic, Olivier Félician, Lejla Koric, Mathieu Ceccaldi, Audrey Gabelle, Cecilia Marelli, Jacques Touchon, Pierre Labauge, Thérèse Jonveaux, Martine Vercelletto, Claire Boutoleau-Bretonnière, Giovanni Castelnovo, David Renaud, Philippe Robert, Claire Paquet, Julien Dumurgier, Jacques Hugon, Foucauld De Boisgueheneuc, Serge Belliard, Serge Bakchine, Marie Sarazin, Marie-Odile Barrellon, Bernard Laurent, Frédéric Blanc, Christine Tranchant, Jérémie Pariente, Michèle Puel, Caroline Hommet, Karl Mondon

Affiliation

¹ From INSERM (K.L.G., G.N., O.Q., C.C., D.W., S.R., A.C.R., A.R.-L., T.F., D.H., D.C.), U1079, IRIB, University of Rouen, Normandy University; Normandy Centre for Genomic Medicine and Personalized Medicine (K.L.G., G.N., O.Q., C.C., D.W., S.R., A.-C.R., A.R.-L., T.F., D.H., D.C.), Rouen; Department of Genetics (G.N., T.F., D.H.), CNR-MAJ (G.N., O.Q., C.C., D.W., S.R., A.-C.R., F.P., A.R.-S., D.H., D.C.), and Department of Neurology (D.W., D.H.), Rouen University Hospital; INSERM (C.B., B.G.-B., P.A., J.-C.L.), U1167, Lille; Institut Pasteur de Lille (C.B., B.G.-B., P.A., J.-C.L.); Université Lille-Nord de France (C.B., B.G.-B., P.A., J.-C.L.); Centre National de Génotypage (D.B., J.-G.G., R.O., A.B., V.M., J.-F.Deleuze.), Institut de Génomique, CEA, Evry; Fondation Jean Dausset (J.-F.Deleuze.), Centre d'Etudes du Polymorphisme Humain, Paris, France; McGill University and Génome Québec Innovation Centre (H.M.M., G.B., M.L.), Montréal, Canada; INSERM (R.R.), UMR 1087, l'Institut du Thorax, CHU Nantes; CNRS (R.R.), UMR 6291, Université de Nantes; INSERM (L.L., J.-F.Dartigues.), U897, Bordeaux; University of Bordeaux (L.L., J.-F.Dartigues.); Department of Neurology (F.P., A.R.S.), Lille University Hospital; INSERM (E.G.), UMR1078, CHU Brest, Université Bretagne Occidentale, Brest; and Department of Research (D.C.), Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France.

PMID: 27037229
PMCID: PMC4898320
DOI: 10.1212/WNL.0000000000002627

Meta-Analysis

ABCA7 rare variants and Alzheimer disease risk

Kilan Le Guennec et al. Neurology. 2016.

. 2016 Jun 7;86(23):2134-7.

doi: 10.1212/WNL.0000000000002627. Epub 2016 Apr 1.

Authors

Collaborators

CNR-MAJ collaborators:
Didier Hannequin, Dominique Campion, David Wallon, Olivier Martinaud, Gaël Nicolas, Adeline Rollin-Sillaire, Stéphanie Bombois, Marie-Anne Mackowiak, Vincent Deramecourt, Florence Pasquier, Agnès Michon, Isabelle Le Ber, Bruno Dubois, Charles Duyckaerts, Olivier Godefroy, Frédérique Etcharry-Bouyx, Valérie Chauviré, Ludivine Chamard, Eric Berger, Eloi Magnin, Jean-Francois Dartigues, Sophie Auriacombe, François Tison, Cyril Goizet, Vincent de la Sayette, Fausto Viader, Dominique Castan, Elsa Dionet, Francois Sellal, Olivier Rouaud, Christel Thauvin, Olivier Moreaud, Mathilde Sauvée, Maïté Formaglio, Hélène Mollion, Isabelle Roullet-Solignac, Alain Vighetto, Bernard Croisile, Mira Didic, Olivier Félician, Lejla Koric, Mathieu Ceccaldi, Audrey Gabelle, Cecilia Marelli, Jacques Touchon, Pierre Labauge, Thérèse Jonveaux, Martine Vercelletto, Claire Boutoleau-Bretonnière, Giovanni Castelnovo, David Renaud, Philippe Robert, Claire Paquet, Julien Dumurgier, Jacques Hugon, Foucauld De Boisgueheneuc, Serge Belliard, Serge Bakchine, Marie Sarazin, Marie-Odile Barrellon, Bernard Laurent, Frédéric Blanc, Christine Tranchant, Jérémie Pariente, Michèle Puel, Caroline Hommet, Karl Mondon

Affiliation

¹ From INSERM (K.L.G., G.N., O.Q., C.C., D.W., S.R., A.C.R., A.R.-L., T.F., D.H., D.C.), U1079, IRIB, University of Rouen, Normandy University; Normandy Centre for Genomic Medicine and Personalized Medicine (K.L.G., G.N., O.Q., C.C., D.W., S.R., A.-C.R., A.R.-L., T.F., D.H., D.C.), Rouen; Department of Genetics (G.N., T.F., D.H.), CNR-MAJ (G.N., O.Q., C.C., D.W., S.R., A.-C.R., F.P., A.R.-S., D.H., D.C.), and Department of Neurology (D.W., D.H.), Rouen University Hospital; INSERM (C.B., B.G.-B., P.A., J.-C.L.), U1167, Lille; Institut Pasteur de Lille (C.B., B.G.-B., P.A., J.-C.L.); Université Lille-Nord de France (C.B., B.G.-B., P.A., J.-C.L.); Centre National de Génotypage (D.B., J.-G.G., R.O., A.B., V.M., J.-F.Deleuze.), Institut de Génomique, CEA, Evry; Fondation Jean Dausset (J.-F.Deleuze.), Centre d'Etudes du Polymorphisme Humain, Paris, France; McGill University and Génome Québec Innovation Centre (H.M.M., G.B., M.L.), Montréal, Canada; INSERM (R.R.), UMR 1087, l'Institut du Thorax, CHU Nantes; CNRS (R.R.), UMR 6291, Université de Nantes; INSERM (L.L., J.-F.Dartigues.), U897, Bordeaux; University of Bordeaux (L.L., J.-F.Dartigues.); Department of Neurology (F.P., A.R.S.), Lille University Hospital; INSERM (E.G.), UMR1078, CHU Brest, Université Bretagne Occidentale, Brest; and Department of Research (D.C.), Rouvray Psychiatric Hospital, Sotteville-lès-Rouen, France.

PMID: 27037229
PMCID: PMC4898320
DOI: 10.1212/WNL.0000000000002627

Abstract

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.

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Comment in

Rare ABCA7 variants in Alzheimer disease: Guilt by association.
Swerdlow RH. Swerdlow RH. Neurology. 2016 Jun 7;86(23):2118-9. doi: 10.1212/WNL.0000000000002630. Epub 2016 Apr 1. Neurology. 2016. PMID: 27037231 No abstract available.

References

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ABCA7 rare variants and Alzheimer disease risk

Collaborators

Affiliation

ABCA7 rare variants and Alzheimer disease risk

Authors

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Affiliation

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