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

  • Author(s): Jun, Gyungah R
  • Chung, Jaeyoon
  • Mez, Jesse
  • Barber, Robert
  • Beecham, Gary W
  • Bennett, David A
  • Buxbaum, Joseph D
  • Byrd, Goldie S
  • Carrasquillo, Minerva M
  • Crane, Paul K
  • Cruchaga, Carlos
  • De Jager, Philip
  • Ertekin-Taner, Nilufer
  • Evans, Denis
  • Fallin, M Danielle
  • Foroud, Tatiana M
  • Friedland, Robert P
  • Goate, Alison M
  • Graff-Radford, Neill R
  • Hendrie, Hugh
  • Hall, Kathleen S
  • Hamilton-Nelson, Kara L
  • Inzelberg, Rivka
  • Kamboh, M Ilyas
  • Kauwe, John SK
  • Kukull, Walter A
  • Kunkle, Brian W
  • Kuwano, Ryozo
  • Larson, Eric B
  • Logue, Mark W
  • Manly, Jennifer J
  • Martin, Eden R
  • Montine, Thomas J
  • Mukherjee, Shubhabrata
  • Naj, Adam
  • Reiman, Eric M
  • Reitz, Christiane
  • Sherva, Richard
  • St George-Hyslop, Peter H
  • Thornton, Timothy
  • Younkin, Steven G
  • Vardarajan, Badri N
  • Wang, Li-San
  • Wendlund, Jens R
  • Winslow, Ashley R
  • Alzheimer's Disease Genetics Consortium
  • Haines, Jonathan
  • Mayeux, Richard
  • Pericak-Vance, Margaret A
  • Schellenberg, Gerard
  • Lunetta, Kathryn L
  • Farrer, Lindsay A
  • et al.
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 × 10-8) 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.

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