Novel Loci for Alzheimer Disease Identified by Genome Wide Association Study in Ashkenazi Jews

Li, Donghe; Farrell, John J; Mez, Jesse; Martin, Eden R.; Bush, William S.; Ruiz, Agustin; Boada, Mercè; de Rojas, Itziar; Mayeux, Richard; Haines, Jonathan L.; Vance, Margaret A. Pericak; Wang, Li-San; Schellenberg, Gerard D.; Lunetta, Kathryn L.; Farrer, Lindsay A.

doi:10.1002/alz.13117

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Novel Loci for Alzheimer Disease Identified by Genome Wide Association Study in Ashkenazi Jews

12 2023
By Li, Donghe ; Farrell, John J ; Mez, Jesse ; ...
Source: Alzheimers Dement. 19(12):5550-5562

Public Access Version Available on: December 01, 2024, 12:00 AM

Please check back on the date listed above.

English

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Details:

Alternative Title:

Alzheimers Dement
Personal Author:

Li, Donghe ; Farrell, John J ; Mez, Jesse ; Martin, Eden R. ; Bush, William S. ; ... More +

Li, Donghe ; Farrell, John J ; Mez, Jesse ; Martin, Eden R. ; Bush, William S. ; Ruiz, Agustin ; Boada, Mercè ; de Rojas, Itziar ; Mayeux, Richard ; Haines, Jonathan L. ; Vance, Margaret A. Pericak ; Wang, Li-San ; Schellenberg, Gerard D. ; Lunetta, Kathryn L. ; Farrer, Lindsay A. Less -
Description:

INTRODUCTION:

Most Alzheimer disease (AD) loci were discovered in European ancestry individuals.

METHODS:

We applied principal component analysis using Gaussian mixture models and an Ashkenazi Jewish (AJ) reference genome-wide association study (GWAS) dataset to identify AJs ascertained in GWAS (n=42,682), whole genome sequencing (WGS, n=16,815) and whole exome sequencing (WES, n=20,504) datasets. Association of AD was tested genome-wide (GW) in the GWAS and WGS datasets and exome-wide (EW) in all three datasets (EW). Gene-based analyses were performed using aggregated rare variants.

RESULTS:

In addition to APOE, GW analyses (1,355 cases and 1,661 controls) revealed associations with TREM2 R47H (P=9.66x10−9), rs541586606 near RAB3B (P=5.01x10−8) and rs760573036 between SPOCK3 and ANXA10 (P=6.32x10−8). In EW analyses (1,504 cases and 2,047 controls), study-wide significant association was observed with rs1003710 near SMAP2 (P=1.91x10−7). A significant gene-based association was identified with GIPR (P=7.34x10−7).

DISCUSSION:

Our results highlight the efficacy of founder populations for AD genetic studies.
Subjects:

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Alzheimer Disease Ethnicity Genetic Predisposition To Disease Genome-Wide Association Study Humans Jews Polymorphism, Single Nucleotide
Keywords:

[+]

Alzheimer Disease Ashkenazi Jews Founder Population Genome-wide Association Study
Source:

Alzheimers Dement. 19(12):5550-5562
Pubmed ID:

37260021
Pubmed Central ID:

PMC10689571
Document Type:

Journal Article
Funding:

R01 AG054076/AG/NIA NIH HHSUnited States/ ; HHSN268201100011I/HL/NHLBI NIH HHSUnited States/ ; P30 AG013854/AG/NIA NIH HHSUnited States/ ; HHSN268201100012C/HL/NHLBI NIH HHSUnited States/ ; P30 AG066444/AG/NIA NIH HHSUnited States/ ; ... More +

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urn:sha-512:9523c544da98c97b760d6afd917a3a66c2e3499844defbfe2745b3da73aecb3939a5e01c2f7b87c54f1e6b4464d3d7e40d82b7c5188750b525109013220ccc61
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