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

Research output: Contribution to journal › Article

36 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
Publication status	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

Alzheimer's Disease Genetics Consortium (2017). Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimer's and Dementia, 13(7), 727-738. https://doi.org/10.1016/j.jalz.2016.12.012

@article{9778aeec9df64c69b0cdb3d64ce0b214,

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

author = "{Alzheimer's Disease Genetics Consortium} and Jun, {Gyungah R.} and Jun, {Gyungah R.} and Jaeyoon Chung and Logue, {Mark W.} and Richard Sherva and Farrer, {Lindsay A.} and Jesse Mez and Farrer, {Lindsay A.} 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 Logue, {Mark W.} and Buxbaum, {Joseph D.} and Goate, {Alison M.} and Buxbaum, {Joseph D.} and Buxbaum, {Joseph D.} 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 Carlos Cruchaga and {De Jager}, Philip 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 Hugh Hendrie and Hall, {Kathleen S.} and Hall, {Kathleen S.} and Rivka Inzelberg and Kamboh, {M. Ilyas} and Kauwe, {John S.K.} and Kukull, {Walter A.} and Kukull, {Walter A.} and Jeffrey Kaye and Aimee Pierce and Joseph Quinn and Woltjer, {Randall (Randy)}",

year = "2017",

month = "7",

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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 - 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 - 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 - 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

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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

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Access to Document

10.1016/j.jalz.2016.12.012