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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Jun, 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; Fallin, MD; Foroud, TM; Friedland, RP; Goate, AM; Graff-Radford, NR; Hendrie, H; Hall, KS; Hamilton-Nelson, KL; Inzelberg, R; Kamboh, MI; 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; Wang, L-S; Wendlund, JR; Winslow, AR; Alzheimer's Disease Genetics Consortium, ; Haines, J; Mayeux, R; Pericak-Vance, MA; Schellenberg, G; Lunetta, KL; Farrer, LA

Published Date

  • July 2017

Published In

Volume / Issue

  • 13 / 7

Start / End Page

  • 727 - 738

PubMed ID

  • 28183528

Pubmed Central ID

  • 28183528

Electronic International Standard Serial Number (EISSN)

  • 1552-5279

International Standard Serial Number (ISSN)

  • 1552-5260

Digital Object Identifier (DOI)

  • 10.1016/j.jalz.2016.12.012

Language

  • eng