Transethnic genome-wide scan identifies novel Alzheimer's disease loci.
INTRODUCTION: Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. METHODS: We conducted a transethnic genome-wide association study (GWAS) for late-onset AD in Stage 1 sample including whites of European Ancestry, African-Americans, Japanese, and Israeli-Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. RESULTS: Genome-wide significant (GWS) associations in single-nucleotide polymorphism (SNP)-based tests (P < 5 × 10-8) were identified for SNPs in PFDN1/HBEGF, USP6NL/ECHDC3, and BZRAP1-AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence (P < 2.7 × 10-6) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10-6). DISCUSSION: Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.
Duke Scholars
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- Receptors, GABA
- Polymorphism, Single Nucleotide
- Peroxisomal Bifunctional Enzyme
- NFI Transcription Factors
- Molecular Chaperones
- Membrane Glycoproteins
- Humans
- Heparin-binding EGF-like Growth Factor
- Geriatrics
- Genome-Wide Association Study
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Receptors, GABA
- Polymorphism, Single Nucleotide
- Peroxisomal Bifunctional Enzyme
- NFI Transcription Factors
- Molecular Chaperones
- Membrane Glycoproteins
- Humans
- Heparin-binding EGF-like Growth Factor
- Geriatrics
- Genome-Wide Association Study