Transethnic genome-wide scan identifies novel Alzheimer's disease loci.

TitleTransethnic genome-wide scan identifies novel Alzheimer's disease loci.
Publication TypeJournal Article
Year of Publication2017
AuthorsJun GR, Chung J, Mez J, Barber R, Beecham GW, Bennett DA, Buxbaum JD, Byrd GS, Carrasquillo MM, Crane PK, Cruchaga C, De Jager P, Ertekin-Taner N, Evans D, M Fallin D, Foroud TM, Friedland RP, Goate AM, Graff-Radford NR, Hendrie H, Hall KS, Hamilton-Nelson KL, Inzelberg R, M Kamboh I, Kauwe JSK, Kukull WA, Kunkle BW, Kuwano R, Larson EB, Logue MW, Manly JJ, Martin ER, Montine TJ, Mukherjee S, Naj A, Reiman EM, Reitz C, Sherva R, St George-Hyslop PH, Thornton T, Younkin SG, Vardarajan BN, San Wang L-, Wendlund JR, Winslow AR, Haines J, Mayeux R, Pericak-Vance MA, Schellenberg G, Lunetta KL, Farrer LA
Corporate AuthorsAlzheimer's Disease Genetics Consortium
JournalAlzheimers Dement
Volume13
Issue7
Pagination727-738
Date Published2017 Jul
ISSN1552-5279
KeywordsAdaptor Proteins, Signal Transducing, Alzheimer Disease, Apolipoprotein E4, Genetic Predisposition to Disease, Genome-Wide Association Study, GTPase-Activating Proteins, Heparin-binding EGF-like Growth Factor, Humans, Membrane Glycoproteins, Molecular Chaperones, NFI Transcription Factors, Peroxisomal Bifunctional Enzyme, Polymorphism, Single Nucleotide, Receptors, GABA
Abstract

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) 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) for gene-based association in the total sample with a novel locus, TPBG (P = 1.8 × 10).

DISCUSSION: Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

DOI10.1016/j.jalz.2016.12.012
Alternate JournalAlzheimers Dement
PubMed ID28183528
PubMed Central IDPMC5496797
Grant ListP30 AG013854 / AG / NIA NIH HHS / United States
P30 AG053760 / AG / NIA NIH HHS / United States
P50 MH060451 / MH / NIMH NIH HHS / United States
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R01 AG054060 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
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M01 RR000096 / RR / NCRR NIH HHS / United States
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P01 GM099568 / GM / NIGMS NIH HHS / United States
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P50 NS039764 / NS / NINDS NIH HHS / United States
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