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

Gyungah R. Jun, Jaeyoon Chung, Jesse Mez, Robert Barber, Gary W. Beecham, David A. Bennett, Joseph D. Buxbaum, Gary W Beecham, Minerva M. Carrasquillo, Paul K. Crane, Eden R Martin, Margaret A Pericak-Vance, Nilufer Ertekin-Taner, Denis Evans, M. Danielle Fallin, Tatiana M. Foroud, Robert P. Friedland, Alison M. Goate, Neill R. Graff-Radford, Hugh HendrieKathleen S. Hall, Kara L. Hamilton-Nelson, Rivka Inzelberg, M. Ilyas Kamboh, John S K Kauwe, Walter A. Kukull, Brian W. Kunkle, Ryozo Kuwano, Eric B. Larson, Mark W. Logue, Jennifer J. Manly, Eden R. Martin, Thomas J. Montine, Shubhabrata Mukherjee, Adam Naj, Eric M. Reiman, Christiane Reitz, Richard Sherva, Peter H. St. George-Hyslop, Timothy Thornton, Steven G. Younkin, Badri N. Vardarajan, Li San Wang, Jens R. Wendlund, Ashley R. Winslow, Jonathan Haines, Richard Mayeux, Margaret A. Pericak-Vance, Gerard Schellenberg, Kathryn L. Lunetta, Clinton B Wright

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 e(open)4 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 languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - 2017

Fingerprint

Alzheimer Disease
Genome
Single Nucleotide Polymorphism
Genome-Wide Association Study
Genetic Loci
Disease Susceptibility
Apolipoproteins E
Genomics
African Americans
Alleles
Population
Genes

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

Jun, G. R., Chung, J., Mez, J., Barber, R., Beecham, G. W., Bennett, D. A., ... Wright, C. B. (Accepted/In press). Transethnic genome-wide scan identifies novel Alzheimer's disease loci. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2016.12.012

Transethnic genome-wide scan identifies novel Alzheimer's disease loci. / Jun, Gyungah R.; Chung, Jaeyoon; Mez, Jesse; Barber, Robert; Beecham, Gary W.; Bennett, David A.; Buxbaum, Joseph D.; Beecham, Gary W; Carrasquillo, Minerva M.; Crane, Paul K.; Martin, Eden R; Pericak-Vance, Margaret A; Ertekin-Taner, Nilufer; Evans, Denis; Fallin, M. Danielle; Foroud, Tatiana M.; Friedland, Robert P.; Goate, Alison M.; Graff-Radford, Neill R.; Hendrie, Hugh; Hall, Kathleen S.; Hamilton-Nelson, Kara L.; Inzelberg, Rivka; Kamboh, M. Ilyas; Kauwe, John S K; Kukull, Walter A.; Kunkle, Brian W.; Kuwano, Ryozo; Larson, Eric B.; Logue, Mark W.; Manly, Jennifer J.; Martin, Eden R.; Montine, Thomas J.; Mukherjee, Shubhabrata; Naj, Adam; Reiman, Eric M.; Reitz, Christiane; Sherva, Richard; St. George-Hyslop, Peter H.; Thornton, Timothy; Younkin, Steven G.; Vardarajan, Badri N.; Wang, Li San; Wendlund, Jens R.; Winslow, Ashley R.; Haines, Jonathan; Mayeux, Richard; Pericak-Vance, Margaret A.; Schellenberg, Gerard; Lunetta, Kathryn L.; Wright, Clinton B.

In: Alzheimer's and Dementia, 2017.

Research output: Contribution to journalArticle

Jun, GR, Chung, J, Mez, J, Barber, R, Beecham, GW, Bennett, DA, Buxbaum, JD, Beecham, GW, Carrasquillo, MM, Crane, PK, Martin, ER, Pericak-Vance, MA, Ertekin-Taner, N, Evans, D, Fallin, MD, Foroud, TM, Friedland, RP, Goate, AM, Graff-Radford, NR, Hendrie, H, Hall, KS, Hamilton-Nelson, KL, Inzelberg, R, Kamboh, MI, Kauwe, JSK, Kukull, WA, Kunkle, BW, Kuwano, R, Larson, EB, Logue, MW, Manly, JJ, Martin, ER, Montine, TJ, Mukherjee, S, Naj, A, Reiman, EM, Reitz, C, Sherva, R, St. George-Hyslop, PH, Thornton, T, Younkin, SG, Vardarajan, BN, Wang, LS, Wendlund, JR, Winslow, AR, Haines, J, Mayeux, R, Pericak-Vance, MA, Schellenberg, G, Lunetta, KL & Wright, CB 2017, 'Transethnic genome-wide scan identifies novel Alzheimer's disease loci', Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2016.12.012
Jun, Gyungah R. ; Chung, Jaeyoon ; Mez, Jesse ; Barber, Robert ; Beecham, Gary W. ; Bennett, David A. ; Buxbaum, Joseph D. ; Beecham, Gary W ; Carrasquillo, Minerva M. ; Crane, Paul K. ; Martin, Eden R ; Pericak-Vance, Margaret A ; Ertekin-Taner, Nilufer ; Evans, Denis ; Fallin, M. Danielle ; Foroud, Tatiana M. ; Friedland, Robert P. ; Goate, Alison M. ; Graff-Radford, Neill R. ; Hendrie, Hugh ; Hall, Kathleen S. ; Hamilton-Nelson, Kara L. ; Inzelberg, Rivka ; Kamboh, M. Ilyas ; Kauwe, John S K ; Kukull, Walter A. ; Kunkle, Brian W. ; Kuwano, Ryozo ; Larson, Eric B. ; Logue, Mark W. ; Manly, Jennifer J. ; Martin, Eden R. ; Montine, Thomas J. ; Mukherjee, Shubhabrata ; Naj, Adam ; Reiman, Eric M. ; Reitz, Christiane ; Sherva, Richard ; St. George-Hyslop, Peter H. ; Thornton, Timothy ; Younkin, Steven G. ; Vardarajan, Badri N. ; Wang, Li San ; Wendlund, Jens R. ; Winslow, Ashley R. ; Haines, Jonathan ; Mayeux, Richard ; Pericak-Vance, Margaret A. ; Schellenberg, Gerard ; Lunetta, Kathryn L. ; Wright, Clinton B. / Transethnic genome-wide scan identifies novel Alzheimer's disease loci. In: Alzheimer's and Dementia. 2017.
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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 e(open)4 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.",
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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 - Mez, Jesse

AU - Barber, Robert

AU - Beecham, Gary W.

AU - Bennett, David A.

AU - Buxbaum, Joseph D.

AU - Beecham, Gary W

AU - Carrasquillo, Minerva M.

AU - Crane, Paul K.

AU - Martin, Eden R

AU - Pericak-Vance, Margaret A

AU - Ertekin-Taner, Nilufer

AU - Evans, Denis

AU - Fallin, M. Danielle

AU - Foroud, Tatiana M.

AU - Friedland, Robert P.

AU - Goate, Alison M.

AU - Graff-Radford, Neill R.

AU - Hendrie, Hugh

AU - Hall, Kathleen S.

AU - Hamilton-Nelson, Kara L.

AU - Inzelberg, Rivka

AU - Kamboh, M. Ilyas

AU - Kauwe, John S K

AU - Kukull, Walter A.

AU - Kunkle, Brian W.

AU - Kuwano, Ryozo

AU - Larson, Eric B.

AU - Logue, Mark W.

AU - Manly, Jennifer J.

AU - Martin, Eden R.

AU - Montine, Thomas J.

AU - Mukherjee, Shubhabrata

AU - Naj, Adam

AU - Reiman, Eric M.

AU - Reitz, Christiane

AU - Sherva, Richard

AU - St. George-Hyslop, Peter H.

AU - Thornton, Timothy

AU - Younkin, Steven G.

AU - Vardarajan, Badri N.

AU - Wang, Li San

AU - Wendlund, Jens R.

AU - Winslow, Ashley R.

AU - Haines, Jonathan

AU - Mayeux, Richard

AU - Pericak-Vance, Margaret A.

AU - Schellenberg, Gerard

AU - Lunetta, Kathryn L.

AU - Wright, Clinton B

PY - 2017

Y1 - 2017

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 e(open)4 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 e(open)4 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

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

SN - 1552-5260

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