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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 727-738 |
| Number of pages | 12 |
| Journal | Alzheimer's and Dementia |
| Volume | 13 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 1 2017 |
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Keywords
- Alzheimer's disease
- APOE interaction
- Genome-wide association
- Transethnic
ASJC Scopus subject areas
- Epidemiology
- Health Policy
- Developmental Neuroscience
- Geriatrics and Gerontology
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Psychiatry and Mental health
Cite this
Transethnic genome-wide scan identifies novel Alzheimer's disease loci. / Alzheimer's Disease Genetics Consortium.
In: Alzheimer's and Dementia, Vol. 13, No. 7, 01.07.2017, p. 727-738.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Transethnic genome-wide scan identifies novel Alzheimer's disease loci
AU - Alzheimer's Disease Genetics Consortium
AU - Jun, Gyungah R.
AU - Jun, Gyungah R.
AU - Chung, Jaeyoon
AU - Logue, Mark W.
AU - Sherva, Richard
AU - Farrer, Lindsay A.
AU - Mez, Jesse
AU - Farrer, Lindsay A.
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 - Logue, Mark W.
AU - Buxbaum, Joseph D.
AU - Goate, Alison M.
AU - Buxbaum, Joseph D.
AU - Buxbaum, Joseph D.
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 - Cruchaga, Carlos
AU - De Jager, Philip
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 - Hendrie, Hugh
AU - Hall, Kathleen S.
AU - Hall, Kathleen S.
AU - Inzelberg, Rivka
AU - Kamboh, M. Ilyas
AU - Kauwe, John S.K.
AU - Kukull, Walter A.
AU - Kukull, Walter A.
AU - Kaye, Jeffrey
AU - Pierce, Aimee
AU - Quinn, Joseph
AU - Woltjer, Randall (Randy)
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 - Alzheimer's disease
KW - APOE interaction
KW - Genome-wide association
KW - Transethnic
UR - http://www.scopus.com/inward/record.url?scp=85014178309&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.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
VL - 13
SP - 727
EP - 738
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 7
ER -