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DOI 10.1016/j.jalz.2016.12.012

Медицинская библиотека · Alzheimer's & dementia : the journal of the Alzheimer's Association · 2017

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

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 S K, 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

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Аннотация

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.

Для цитирования: 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 S K, 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. Transethnic genome-wide scan identifies novel Alzheimer's disease loci.. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2017. DOI: 10.1016/j.jalz.2016.12.012.

Предметные рубрики MeSH

Adaptor Proteins, Signal TransducingAlzheimer DiseaseApolipoprotein E4GTPase-Activating ProteinsGenetic Predisposition to DiseaseGenome-Wide Association StudyHeparin-binding EGF-like Growth FactorHumansMembrane GlycoproteinsMolecular ChaperonesNFI Transcription FactorsPeroxisomal Bifunctional EnzymePolymorphism, Single NucleotideReceptors, GABA
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