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Contribution to Alzheimer's disease risk of rare variants in TREM2, SORL1, and ABCA7 in 1779 cases and 1273 controls.
- Source :
-
Neurobiology of aging [Neurobiol Aging] 2017 Nov; Vol. 59, pp. 220.e1-220.e9. Date of Electronic Publication: 2017 Jul 14. - Publication Year :
- 2017
-
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 <superscript>-6</superscript> 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.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Apolipoprotein E4 genetics
Female
Humans
Male
Middle Aged
Whole Genome Sequencing
Young Adult
ATP-Binding Cassette Transporters genetics
Alzheimer Disease genetics
Genetic Association Studies
Genetic Predisposition to Disease genetics
Genetic Variation genetics
Genome-Wide Association Study
LDL-Receptor Related Proteins genetics
Membrane Glycoproteins genetics
Membrane Transport Proteins genetics
Receptors, Immunologic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1558-1497
- Volume :
- 59
- Database :
- MEDLINE
- Journal :
- Neurobiology of aging
- Publication Type :
- Academic Journal
- Accession number :
- 28789839
- Full Text :
- https://doi.org/10.1016/j.neurobiolaging.2017.07.001