Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls
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1
Céline Bellenguez
- Function : Author
Camille Charbonnier
- Function : Author
Benjamin Grenier-Boley
- Function : Author
Olivier Quenez
- Function : Author
Kilan Le Guennec
- Function : Author
Gaël Nicolas
- Function : Author
- PersonId : 9291
- IdHAL : gael-nicolas
- ORCID : 0000-0002-1671-8274
- IdRef : 08351483X
Ganesh Chauhan
- Function : Author
David Wallon
- Function : Author
Stéphane Rousseau
- Function : Author
- PersonId : 178973
- IdHAL : laure-guilhaudis
- ORCID : 0000-0002-6212-9593
- IdRef : 230659403
Anne Claire Richard
- Function : Author
Anne Boland
- Function : Author
- PersonId : 757786
- ORCID : 0000-0001-8789-5676
Guillaume Bourque
- Function : Author
Hans Markus Munter
- Function : Author
Robert Olaso
- Function : Author
- PersonId : 774936
- ORCID : 0000-0001-7631-9657
Vincent Meyer
- Function : Author
Adeline Rollin-Sillaire
- Function : Author
Florence Pasquier
- Function : Author
Luc Letenneur
- Function : Author
Richard Redon
- Function : Author
- PersonId : 758188
- ORCID : 0000-0001-7751-2280
- IdRef : 069236984
Jean-François Dartigues
- Function : Author
Christophe Tzourio
- Function : Author
- PersonId : 758563
- ORCID : 0000-0002-6517-2984
- IdRef : 069829209
Thierry Frebourg
- Function : Author
Mark Lathrop
- Function : Author
Jean-François Deleuze
- Function : Author
- PersonId : 798476
- ORCID : 0000-0002-5358-4463
Didier Hannequin
- Function : Author
Emmanuelle Genin
- Function : Author
Philippe Amouyel
- Function : Author
- PersonId : 756626
- ORCID : 0000-0001-9088-234X
- IdRef : 058556818
Stéphanie Debette
- Function : Author
- PersonId : 759687
- ORCID : 0000-0001-8675-7968
- IdRef : 104485833
Jean-Charles Lambert
- Function : Author
- PersonId : 757776
- ORCID : 0000-0003-0829-7817
- IdRef : 12491506X
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
- Function : Author
- PersonId : 901333
- ORCID : 0000-0001-6789-6620
- IdRef : 068994737
Frédérique Etcharry-Bouyx
- Function : Author
- PersonId : 992844
Valérie Chauviré
- Function : Author
Ludivine Chamard
- Function : Author
Eric Berger
- Function : Author
Eloi Magnin
- Function : Author
- PersonId : 773699
- ORCID : 0000-0003-3036-9266
- IdRef : 144716755
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
- Function : Author
- PersonId : 170297
- IdHAL : olivier-rouaud
- ORCID : 0000-0003-1640-9954
- IdRef : 067132049
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
- Function : Author
- PersonId : 757436
- ORCID : 0000-0001-7067-536X
Olivier Félician
- Function : Author
Lejla Koric
- Function : Author
Mathieu Ceccaldi
- Function : Author
- PersonId : 757312
- ORCID : 0000-0002-4924-6736
Audrey Gabelle
- Function : Author
- PersonId : 757644
- ORCID : 0000-0002-7648-9194
Cecilia Marelli
- Function : Author
Pierre Labauge
- Function : Author
- PersonId : 759958
- ORCID : 0000-0001-7759-8555
- IdRef : 059860367
Thérèse Jonveaux
- Function : Author
Martine Vercelletto
- Function : Author
Claire Boutoleau-Bretonnière
- Function : Author
Giovanni Castelnovo
- Function : Author
Claire Paquet
- Function : Author
Julien Dumurgier
- Function : Author
- PersonId : 764398
- ORCID : 0000-0003-2070-9706
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
- Function : Author
- PersonId : 777350
- ORCID : 0000-0002-6714-3247
- IdRef : 153058056
Jérémie Pariente
- Function : Author
Snejana Jurici
- Function : Author
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.