- Home
- About
- Collaborative Data Access (SAGs)
- Publications
- For Members
Title | Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews. |
Publication Type | Journal Article |
Year of Publication | 2023 |
Authors | Li D, Farrell JJ, Mez J, Martin ER, Bush WS, Ruiz A, Boada M, de Rojas I, Mayeux R, Haines JL, Vance MAPericak, San Wang L-, Schellenberg GD, Lunetta KL, Farrer LA |
Journal | Alzheimers Dement |
Date Published | 06/2023 |
ISSN | 1552-5279 |
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 ), rs541586606 near RAB3B (p = 5.01 × 10 ), and rs760573036 between SPOCK3 and ANXA10 (p = 6.32 × 10 ). In EW analyses (1504 cases and 2047 controls), study-wide significant association was observed with rs1003710 near SMAP2 (p = 1.91 × 10 ). A significant gene-based association was identified with GIPR (p = 7.34 × 10 ). DISCUSSION: Our results highlight the efficacy of founder populations for AD genetic studies. |
DOI | 10.1002/alz.13117 |
Alternate Journal | Alzheimers Dement |
PubMed ID | 37260021 |
Grant List | P30 AG072978 / AG / NIA NIH HHS / United States RF1-AG057519 / AG / NIA NIH HHS / United States R01-AG048927 / AG / NIA NIH HHS / United States U01 AG032984 / AG / NIA NIH HHS / United States U54-AG052427 / AG / NIA NIH HHS / United States P30-AG072878 / AG / NIA NIH HHS / United States U19 AG068753 / AG / NIA NIH HHS / United States U01 AG058654 / AG / NIA NIH HHS / United States U01-AG062602 / AG / NIA NIH HHS / United States U01-AG058654 / AG / NIA NIH HHS / United States U01-AG032984 / AG / NIA NIH HHS / United States U19-AG068753 / AG / NIA NIH HHS / United States |