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Bellenguez, Céline; Charbonnier, Camille; Grenier-Boley, Benjamin; Quenez, Olivier; Le Guennec, Kilan; Nicolas, Gaël; Chauhan, Ganesh; Wallon, David; Rousseau, Stéphane; Richard, Anne Claire; Boland, Anne; Bourque, Guillaume; Munter, Hans Markus; Olaso, Robert; Meyer, Vincent; Rollin-Sillaire, Adeline; Pasquier, Florence; Letenneur, Luc; Redon, Richard; Dartigues, Jean-François; Tzourio, Christophe; Frebourg, Thierry; Lathrop, Mark; Deleuze, Jean-François; Hannequin, Didier; Genin, Emmanuelle; Amouyel, Philippe; Debette, Stéphanie; Lambert, Jean-Charles; Campion, Dominique; Hannequin, Didier; Campion, Dominique; Wallon, David; Martinaud, Olivier; Zarea, Aline; Nicolas, Gaël; Rollin-Sillaire, Adeline; Bombois, Stéphanie; Mackowiak, Marie-Anne; Deramecourt, Vincent; Pasquier, Florence; Michon, Agnès; Le Ber, Isabelle; Dubois, Bruno; Godefroy, Olivier; Etcharry-Bouyx, Frédérique; Chauviré, Valérie; Chamard, Ludivine; Berger, Eric; Magnin, Eloi; Dartigues, Jean-Francois; Auriacombe, Sophie; Tison, François; Sayette, Vincent de la; Castan, Dominique; Dionet, Elsa; Sellal, Francois; Rouaud, Olivier; Thauvin, Christel; Moreaud, Olivier; Sauvée, Mathilde; Formaglio, Maïté; Mollion, Hélène; Roullet-Solignac, Isabelle; Vighetto, Alain; Croisile, Bernard; Didic, Mira; Félician, Olivier; Koric, Lejla; Ceccaldi, Mathieu; Gabelle, Audrey; Marelli, Cecilia; Labauge, Pierre; Jonveaux, Thérèse; Vercelletto, Martine; Boutoleau-Bretonnière, Claire; Castelnovo, Giovanni; Paquet, Claire; Dumurgier, Julien; Hugon, Jacques; De Boisgueheneuc, Foucauld; Belliard, Serge; Bakchine, Serge; Sarazin, Marie; Barrellon, Marie-Odile; Laurent, Bernard; Blanc, Frédéric; Pariente, Jérémie; Jurici, Snejana
Neurobiology of aging, November 2017, 2017-11-00, 20171101, Letnik: 59Journal Article
We performed whole-exome and whole-genome sequencing in 927 late-onset Alzheimer disease (LOAD) cases, 852 early-onset AD (EOAD) cases, and 1273 controls from France. We assessed the evidence for gene-based association of rare variants with AD in 6 genes for which an association with such variants was previously claimed. When aggregating protein-truncating and missense-predicted damaging variants, we found exome-wide significant association between EOAD risk and rare variants in SORL1, TREM2, and ABCA7. No exome-wide significant signal was obtained in the LOAD sample, and significance of the order of 10−6 was observed in the whole AD group for TREM2. Our study confirms previous gene-level results for TREM2, SORL1, and ABCA7 and provides a clearer insight into the classes of rare variants involved. Despite different effect sizes and varying cumulative minor allele frequencies, the rare protein-truncating and missense-predicted damaging variants in TREM2, SORL1, and ABCA7 contribute similarly to the heritability of EOAD and explain between 1.1% and 1.5% of EOAD heritability each, compared with 9.12% for APOE ε4.
