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

doi:10.1016/j.jalz.2016.12.012

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

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

129 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
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

Bibliographical note

Publisher Copyright:
© 2017 The Authors

Funding

Funders	Funder number
National Institute of Mental Health	P50MH060451, R01MH080295
National Institute of Mental Health
National Institute on Aging	R01AG033193, P50AG005146, RC2AG036535, R01AG048927, P50AG005142, RF1AG054023, U01AG024904, U24AG021886, R01AG019085, R01AG025259, P30AG053760, U01AG016976, P01AG010491, P50AG005133, RC2AG036528, P01AG000538, P50AG005134, P50AG005131, R01AG054060, K01AG030514, P30AG013854, RF1AG051504, K23AG046377, P30AG028383, R01AG027944, P50AG016582, R01AG034504, U01AG010483, P50AG005136, P50AG025688, P50AG005138, P50AG023501, R01AG021547, P50AG005681, P50AG008671, P30AG028377, R37AG015473, R01AG026916, P01AG019724, R01AG030146, U01AG006781, P50AG016573, P50AG016574, P30AG010133, P30AG013846, R01AG030653, P50AG016570, R01AG017917, P01AG002219, P50AG005128, R01AG015819, U01AG032984, R01AG019757, R01AG026390, R01AG020688, R01AG017173, P30AG008017, R01AG031581, U24AG026395, P30AG010124, P30AG012300, P30AG010161, P01AG003991, P30AG010129, P30AG019610, P30AG008051, P50AG008702
National Institute on Aging
National Human Genome Research Institute	U01HG006375, U01HG004610
National Human Genome Research Institute
National Childhood Cancer Registry – National Cancer Institute	R01CA129769
National Childhood Cancer Registry – National Cancer Institute
National Institute of General Medical Sciences	P01GM099568
National Institute of General Medical Sciences
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council	R01NS059873, P50NS039764
Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council
National Center for Research Resources	M01RR000096, UL1RR029893
National Center for Research Resources
National Center for Advancing Translational Sciences (NCATS)	UL1TR001445
National Center for Advancing Translational Sciences (NCATS)
Medical Research Council	G1001253, MR/K01417X/1, MR/J004758/1, G0901254
Medical Research Council
Japan Society for the Promotion of Science	16K14649
Japan Society for the Promotion of Science

Keywords

APOE interaction
Alzheimer's disease
Genome-wide association
Transethnic

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jalz.2016.12.012

Cite this

@article{6e225f8f88ed487b9bd75daf750e6112,

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 = "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 Jicha, {Gregory A.} and {Van Eldik}, {Linda J.}",

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

year = "2017",

month = jul,

day = "1",

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

language = "English",

volume = "13",

pages = "727--738",

number = "7",

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TY - JOUR

T1 - Transethnic genome-wide scan identifies novel Alzheimer's disease loci

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 - Jicha, Gregory A.

AU - Van Eldik, Linda J.

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

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DO - 10.1016/j.jalz.2016.12.012

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SN - 1552-5260

VL - 13

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EP - 738

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

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ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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