Multi-ancestry meta-analysis and fine-mapping in Alzheimer's disease.
Humans
Alzheimer Disease
/ ethnology
Black or African American
/ genetics
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
/ methods
Genotype
Polymorphism, Single Nucleotide
/ genetics
East Asian People
/ genetics
European People
/ genetics
Caribbean People
/ genetics
Hispanic or Latino
/ genetics
South American People
/ genetics
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
received:
20
10
2022
accepted:
31
03
2023
revised:
27
03
2023
medline:
1
11
2023
pubmed:
18
5
2023
entrez:
17
5
2023
Statut:
ppublish
Résumé
Genome-wide association studies (GWAS) of Alzheimer's disease are predominantly carried out in European ancestry individuals despite the known variation in genetic architecture and disease prevalence across global populations. We leveraged published GWAS summary statistics from European, East Asian, and African American populations, and an additional GWAS from a Caribbean Hispanic population using previously reported genotype data to perform the largest multi-ancestry GWAS meta-analysis of Alzheimer's disease and related dementias to date. This method allowed us to identify two independent novel disease-associated loci on chromosome 3. We also leveraged diverse haplotype structures to fine-map nine loci with a posterior probability >0.8 and globally assessed the heterogeneity of known risk factors across populations. Additionally, we compared the generalizability of multi-ancestry- and single-ancestry-derived polygenic risk scores in a three-way admixed Colombian population. Our findings highlight the importance of multi-ancestry representation in uncovering and understanding putative factors that contribute to risk of Alzheimer's disease and related dementias.
Identifiants
pubmed: 37198259
doi: 10.1038/s41380-023-02089-w
pii: 10.1038/s41380-023-02089-w
pmc: PMC10615750
doi:
Types de publication
Meta-Analysis
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3121-3132Subventions
Organisme : NIA NIH HHS
ID : R01 AG062588
Pays : United States
Organisme : NINDS NIH HHS
ID : U54 NS123985
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG062422
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA NS003154
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AG000949
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG057234
Pays : United States
Informations de copyright
© 2023. The Author(s).
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