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

Alzheimer's Disease Genetics Consortium

doi:10.1016/j.jalz.2016.12.012

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

Alzheimer's Disease Genetics Consortium

School of Environmental and Biological Sciences, Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

126 Scopus citations

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	https://doi.org/10.1016/j.jalz.2016.12.012
State	Published - Jul 1 2017

All Science Journal Classification (ASJC) codes

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

Keywords

APOE interaction
Alzheimer's disease
Genome-wide association
Transethnic

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10.1016/j.jalz.2016.12.012

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@article{8718cf2504584c27abd0358d5734f628,

title = "Transethnic genome-wide scan identifies novel Alzheimer's disease loci",

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.",

keywords = "APOE interaction, Alzheimer's disease, Genome-wide association, Transethnic",

author = "{Alzheimer's Disease Genetics Consortium} and Jun, {Gyungah R.} and Jaeyoon Chung and Logue, {Mark W.} and Richard Sherva and Farrer, {Lindsay A.} and Jesse Mez and Robert Barber and Beecham, {Gary W.} and Hamilton-Nelson, {Kara L.} and Kunkle, {Brian W.} and Martin, {Eden R.} and Pericak-Vance, {Margaret A.} and Bennett, {David A.} and Buxbaum, {Joseph D.} and Goate, {Alison M.} and Alison Goate and M. Carlos and Byrd, {Goldie S.} and Carrasquillo, {Minerva M.} and Nilufer Ertekin-Taner and Graff-Radford, {Neill R.} and Younkin, {Steven G.} and Crane, {Paul K.} and Shubhabrata Mukherjee and Timothy Thornton and Carlos Cruchaga and {De Jager}, Philip and Larson, {Eric B.} and Denis Evans and Fallin, {M. Danielle} and Foroud, {Tatiana M.} and Friedland, {Robert P.} and Hugh Hendrie and Hall, {Kathleen S.} and Rivka Inzelberg and Kamboh, {M. Ilyas} and Kauwe, {John S.K.} and Kukull, {Walter A.} and Adams, {Perrie M.} and Ryozo Kuwano and Albin, {Roger L.} and Apostolova, {Liana G.} and Manly, {Jennifer J.} and Vardarajan, {Badri N.} and Richard Mayeux and Barmada, {Michjael M.} and Barnes, {Lisa L.} and Beach, {Thomas G.} and Montine, {Thomas J.} and Miller, {Joshua W.}",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = jul,

day = "1",

doi = "10.1016/j.jalz.2016.12.012",

language = "English (US)",

volume = "13",

pages = "727--738",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

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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 - Montine, Thomas J.

AU - Miller, Joshua W.

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

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

SN - 1552-5260

VL - 13

SP - 727

EP - 738

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 7

ER -

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

Abstract

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