Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls - Archive ouverte HAL Access content directly
Journal Articles Neurobiology of Aging Year : 2017

Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls

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Céline Bellenguez
  • Function : Author
Camille Charbonnier
  • Function : Author
Benjamin Grenier-Boley
  • Function : Author
Olivier Quenez
  • Function : Author
Kilan Le Guennec
  • Function : Author
Gaël Nicolas
Ganesh Chauhan
  • Function : Author
David Wallon
  • Function : Author
Stéphane Rousseau
Anne Claire Richard
  • Function : Author
Anne Boland
Guillaume Bourque
  • Function : Author
Hans Markus Munter
  • Function : Author
Robert Olaso
Vincent Meyer
  • Function : Author
Adeline Rollin-Sillaire
  • Function : Author
Florence Pasquier
  • Function : Author
Luc Letenneur
  • Function : Author
Richard Redon
Jean-François Dartigues
  • Function : Author
Christophe Tzourio
Thierry Frebourg
  • Function : Author
Mark Lathrop
  • Function : Author
Jean-François Deleuze
Didier Hannequin
  • Function : Author
Emmanuelle Genin
  • Function : Author
Philippe Amouyel
Stéphanie Debette
Jean-Charles Lambert
Dominique Campion
  • Function : Author
Olivier Martinaud
  • Function : Author
Aline Zarea
  • Function : Author
Stéphanie Bombois
  • Function : Author
Marie-Anne Mackowiak
  • Function : Author
Vincent Deramecourt
  • Function : Author
Agnès Michon
  • Function : Author
Isabelle Le Ber
  • Function : Author
Bruno Dubois
  • 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
Sophie Auriacombe
  • Function : Author
François Tison
  • Function : Author
Vincent de La Sayette
  • 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
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
Pierre Labauge
Thérèse Jonveaux
  • Function : Author
Martine Vercelletto
  • Function : Author
Claire Boutoleau-Bretonnière
  • Function : Author
Giovanni Castelnovo
  • Function : Author
Claire Paquet
  • Function : Author
Julien Dumurgier
Jacques Hugon
  • Function : Author
Foucauld de Boisgueheneuc
  • Function : Author
Serge Belliard
  • Function : Author
Serge Bakchine
  • Function : Author
Marie Sarazin
  • Function : Author
Marie-Odile Barrellon
  • Function : Author
Bernard Laurent
  • Function : Author
Frédéric Blanc
Jérémie Pariente
  • Function : Author
Snejana Jurici
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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.
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Dates and versions

hal-03630186 , version 1 (04-04-2022)

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Céline Bellenguez, Camille Charbonnier, Benjamin Grenier-Boley, Olivier Quenez, Kilan Le Guennec, et al.. Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls. Neurobiology of Aging, 2017, 59, pp.220.e1-220.e9. ⟨10.1016/j.neurobiolaging.2017.07.001⟩. ⟨hal-03630186⟩

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