Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus.
Alzheimer disease
Chromosome 9
Genetic linkage
Puerto Ricans
Underserved populations
Journal
Neurobiology of aging
ISSN: 1558-1497
Titre abrégé: Neurobiol Aging
Pays: United States
ID NLM: 8100437
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
25
11
2020
revised:
08
02
2021
accepted:
23
02
2021
pubmed:
28
4
2021
medline:
24
12
2021
entrez:
27
4
2021
Statut:
ppublish
Résumé
The genetic admixture of Caribbean Hispanics provides an opportunity to discover novel genetic factors in Alzheimer disease (AD). We sought to identify genetic variants for AD through a family-based design using the Puerto Rican (PR) Alzheimer Disease Initiative (PRADI). Whole-genome sequencing (WGS) and parametric linkage analysis were performed for 100 individuals from 23 multiplex PRADI families. Variants were prioritized by minor allele frequency (<0.01), functional potential [combined annotation dependent depletion score (CADD) >10], and co-segregation with AD. Variants were further ranked using an independent PR case-control WGS dataset (PR10/66). A genome-wide significant linkage peak was found in 9p21 with a heterogeneity logarithm of the odds score (HLOD) >5.1, which overlaps with an AD linkage region from two published independent studies. The region harbors C9orf72, but no expanded repeats were observed in the families. Seven variants prioritized by the PRADI families also displayed evidence for association in the PR10/66 (p < 0.05), including a missense variant in UNC13B. Our study demonstrated the importance of family-based design and WGS in genetic study of AD.
Identifiants
pubmed: 33902942
pii: S0197-4580(21)00074-9
doi: 10.1016/j.neurobiolaging.2021.02.019
pmc: PMC8851406
mid: NIHMS1678494
pii:
doi:
Substances chimiques
C9orf72 Protein
0
C9orf72 protein, human
0
Nerve Tissue Proteins
0
UNC13B protein, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115.e1-115.e7Subventions
Organisme : NIA NIH HHS
ID : U01 AG058654
Pays : United States
Organisme : NIA NIH HHS
ID : RF1 AG054074
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG057659
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG066462
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG070864
Pays : United States
Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
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