Title |
Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls
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Published in |
Neurobiology of Aging, July 2017
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DOI | 10.1016/j.neurobiolaging.2017.07.001 |
Pubmed ID | |
Authors |
Céline Bellenguez, Camille Charbonnier, Benjamin Grenier-Boley, Olivier Quenez, Kilan Le Guennec, Gaël Nicolas, Ganesh Chauhan, David Wallon, Stéphane Rousseau, Anne Claire Richard, Anne Boland, Guillaume Bourque, Hans Markus Munter, Robert Olaso, Vincent Meyer, Adeline Rollin-Sillaire, Florence Pasquier, Luc Letenneur, Richard Redon, Jean-François Dartigues, Christophe Tzourio, Thierry Frebourg, Mark Lathrop, Jean-François Deleuze, Didier Hannequin, Emmanuelle Genin, Philippe Amouyel, Stéphanie Debette, Jean-Charles Lambert, Dominique Campion, CNR MAJ collaborators, Didier Hannequin, Dominique Campion, David Wallon, Olivier Martinaud, Aline Zarea, Gaël Nicolas, Adeline Rollin-Sillaire, Stéphanie Bombois, Marie-Anne Mackowiak, Vincent Deramecourt, Florence Pasquier, Agnès Michon, Isabelle Le Ber, Bruno Dubois, Olivier Godefroy, Frédérique Etcharry-Bouyx, Valérie Chauviré, Ludivine Chamard, Eric Berger, Eloi Magnin, Jean-Francois Dartigues, Sophie Auriacombe, François Tison, Vincent de la Sayette, 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, Pierre Labauge, Thérèse Jonveaux, Martine Vercelletto, Claire Boutoleau-Bretonnière, Giovanni Castelnovo, Claire Paquet, Julien Dumurgier, Jacques Hugon, Foucauld De Boisgueheneuc, Serge Belliard, Serge Bakchine, Marie Sarazin, Marie-Odile Barrellon, Bernard Laurent, Frédéric Blanc, Jérémie Pariente, Snejana Jurici |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 1 | 33% |
Unknown | 2 | 67% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 2 | 67% |
Practitioners (doctors, other healthcare professionals) | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 174 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 35 | 20% |
Researcher | 27 | 16% |
Student > Master | 21 | 12% |
Student > Bachelor | 10 | 6% |
Student > Doctoral Student | 8 | 5% |
Other | 19 | 11% |
Unknown | 54 | 31% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 31 | 18% |
Biochemistry, Genetics and Molecular Biology | 27 | 16% |
Agricultural and Biological Sciences | 22 | 13% |
Medicine and Dentistry | 14 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 2% |
Other | 17 | 10% |
Unknown | 59 | 34% |