TY - JOUR
T1 - Transethnic genome-wide scan identifies novel Alzheimer's disease loci
AU - Alzheimer’s Disease Genetics Consortium
AU - Jun, Gyungah R.
AU - Chung, Jaeyoon
AU - Logue, Mark W.
AU - Sherva, Richard
AU - Farrer, Lindsay A.
AU - Mez, Jesse
AU - Barber, Robert
AU - Beecham, Gary W.
AU - Hamilton-Nelson, Kara L.
AU - Kunkle, Brian W.
AU - Martin, Eden R.
AU - Pericak-Vance, Margaret A.
AU - Bennett, David A.
AU - Buxbaum, Joseph D.
AU - Goate, Alison M.
AU - Goate, Alison
AU - Carlos, M.
AU - Byrd, Goldie S.
AU - Carrasquillo, Minerva M.
AU - Ertekin-Taner, Nilufer
AU - Graff-Radford, Neill R.
AU - Younkin, Steven G.
AU - Crane, Paul K.
AU - Mukherjee, Shubhabrata
AU - Thornton, Timothy
AU - Cruchaga, Carlos
AU - De Jager, Philip
AU - Larson, Eric B.
AU - Evans, Denis
AU - Fallin, M. Danielle
AU - Foroud, Tatiana M.
AU - Friedland, Robert P.
AU - Hendrie, Hugh
AU - Hall, Kathleen S.
AU - Inzelberg, Rivka
AU - Kamboh, M. Ilyas
AU - Kauwe, John S.K.
AU - Kukull, Walter A.
AU - Adams, Perrie M.
AU - Kuwano, Ryozo
AU - Albin, Roger L.
AU - Apostolova, Liana G.
AU - Manly, Jennifer J.
AU - Vardarajan, Badri N.
AU - Mayeux, Richard
AU - Barmada, Michjael M.
AU - Barnes, Lisa L.
AU - Beach, Thomas G.
AU - Fairchild, Thomas J.
AU - Olichney, John M.
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/7/1
Y1 - 2017/7/1
N2 - 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.
AB - 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.
KW - APOE interaction
KW - Alzheimer's disease
KW - Genome-wide association
KW - Transethnic
UR - http://www.scopus.com/inward/record.url?scp=85014178309&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2016.12.012
DO - 10.1016/j.jalz.2016.12.012
M3 - Article
C2 - 28183528
AN - SCOPUS:85014178309
SN - 1552-5260
VL - 13
SP - 727
EP - 738
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
IS - 7
ER -