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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
K01 AG030514 / AG / NIA NIH HHS / United States
UL1 TR001445 / TR / NCATS NIH HHS / United States
R01 AG054060 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
U01 HG006375 / HG / NHGRI NIH HHS / United States
M01 RR000096 / RR / NCRR NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
P50 AG008671 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
P50 AG005128 / AG / NIA NIH HHS / United States
P30 AG010133 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
R01 AG031581 / AG / NIA NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
P50 AG005146 / AG / NIA NIH HHS / United States
R01 AG019085 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
P01 GM099568 / GM / NIGMS NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
P01 AG000538 / AG / NIA NIH HHS / United States
UL1 RR029893 / RR / NCRR NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
P50 NS039764 / NS / NINDS NIH HHS / United States
P01 AG003991 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01 MH080295 / MH / NIMH NIH HHS / United States
R01 AG026390 / AG / NIA NIH HHS / United States
RF1 AG054023 / AG / NIA NIH HHS / United States
RC2 AG036535 / AG / NIA NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
P30 AG012300 / AG / NIA NIH HHS / United States
RF1 AG051504 / AG / NIA NIH HHS / United States
P50 AG016573 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
P50 AG016570 / AG / NIA NIH HHS / United States
P50 AG005134 / AG / NIA NIH HHS / United States
P30 AG008017 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
P50 AG025688 / AG / NIA NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
U24 AG026395 / AG / NIA NIH HHS / United States
R01 CA129769 / CA / NCI NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
U01 AG010483 / AG / NIA NIH HHS / United States
P01 AG002219 / AG / NIA NIH HHS / United States
U01 AG006781 / AG / NIA NIH HHS / United States
P01 AG010491 / AG / NIA NIH HHS / United States
K23 AG046377 / AG / NIA NIH HHS / United States
R01 AG034504 / AG / NIA NIH HHS / United States
R01 AG021547 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
R01 AG048927 / AG / NIA NIH HHS / United States
R01 AG019757 / AG / NIA NIH HHS / United States
R01 AG020688 / AG / NIA NIH HHS / United States
R01 AG030653 / AG / NIA NIH HHS / United States
R01 AG027944 / AG / NIA NIH HHS / United States
R01 AG017173 / AG / NIA NIH HHS / United States
R01 AG025259 / AG / NIA NIH HHS / United States
RF1 AG015473 / AG / NIA NIH HHS / United States
U01 HG004610 / HG / NHGRI NIH HHS / United States
/ / Wellcome Trust / United Kingdom
P30 AG010129 / AG / NIA NIH HHS / United States
P30 AG019610 / AG / NIA NIH HHS / United States
P50 AG016582 / AG / NIA NIH HHS / United States
P30 AG028383 / AG / NIA NIH HHS / United States
R01 AG026916 / AG / NIA NIH HHS / United States
R01 NS059873 / NS / NINDS NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States