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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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