Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews.
Alzheimers Dement
; 19(12): 5550-5562, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37260021
ABSTRACT
INTRODUCTION:
Most Alzheimer's disease (AD) loci have been discovered in individuals with European ancestry (EA).METHODS:
We applied principal component analysis using Gaussian mixture models and an Ashkenazi Jewish (AJ) reference genome-wide association study (GWAS) data set to identify Ashkenazi Jews ascertained in GWAS (n = 42,682), whole genome sequencing (WGS, n = 16,815), and whole exome sequencing (WES, n = 20,504) data sets. The association of AD was tested genome wide (GW) in the GWAS and WGS data sets and exome wide (EW) in all three data sets (EW). Gene-based analyses were performed using aggregated rare variants.RESULTS:
In addition to apolipoprotein E (APOE), GW analyses (1355 cases and 1661 controls) revealed associations with TREM2 R47H (p = 9.66 × 10-9 ), rs541586606 near RAB3B (p = 5.01 × 10-8 ), and rs760573036 between SPOCK3 and ANXA10 (p = 6.32 × 10-8 ). In EW analyses (1504 cases and 2047 controls), study-wide significant association was observed with rs1003710 near SMAP2 (p = 1.91 × 10-7 ). A significant gene-based association was identified with GIPR (p = 7.34 × 10-7 ).DISCUSSION:
Our results highlight the efficacy of founder populations for AD genetic studies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Estudo de Associação Genômica Ampla
/
Doença de Alzheimer
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Alzheimers Dement
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos