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The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study design and methodology.
- Source :
-
Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2023 Sep; Vol. 19 (9), pp. 4187-4195. Date of Electronic Publication: 2023 Jun 30. - Publication Year :
- 2023
-
Abstract
- Introduction: Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late-onset AD although early-onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations, resulting in a lack of understanding of its molecular etiology.<br />Methods: Whole-genome sequencing and harmonization of clinical, neuropathological, and biomarker data of over 5000 EOAD cases of diverse ancestries.<br />Results: A publicly available genomics resource for EOAD with extensive harmonized phenotypes. Primary analysis will (1) identify novel EOAD risk loci and druggable targets; (2) assess local-ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits.<br />Discussion: This novel resource complements over 50,000 control and late-onset AD samples generated through the Alzheimer's Disease Sequencing Project (ADSP). The harmonized EOAD/ADSP joint call will be available through upcoming ADSP data releases and will allow for additional analyses across the full onset range.<br />Highlights: Sequencing efforts to identify genetic variants and pathways underlying Alzheimer's disease (AD) have largely focused on late-onset AD although early-onset AD (EOAD), accounting for ∼10% of cases, is largely unexplained by known mutations. This results in a significant lack of understanding of the molecular etiology of this devastating form of the disease. The Early-Onset Alzheimer's Disease Whole-genome Sequencing Project is a collaborative initiative to generate a large-scale genomics resource for early-onset Alzheimer's disease with extensive harmonized phenotype data. Primary analyses are designed to (1) identify novel EOAD risk and protective loci and druggable targets; (2) assess local-ancestry effects; (3) create EOAD prediction models; and (4) assess genetic overlap with cardiovascular and other traits. The harmonized genomic and phenotypic data from this initiative will be available through NIAGADS.<br /> (© 2023 the Alzheimer's Association.)
- Subjects :
- Humans
Mutation genetics
Age of Onset
Alzheimer Disease genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-5279
- Volume :
- 19
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Alzheimer's & dementia : the journal of the Alzheimer's Association
- Publication Type :
- Academic Journal
- Accession number :
- 37390458
- Full Text :
- https://doi.org/10.1002/alz.13370