Transethnic genome‐wide scan identifies novel Alzheimer's disease loci
Open accessAbstract
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.
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The effect of APOEε4 on Alzheimer's disease risk differs across ethnicities.
“the effect of APOEε4 has been reported to differ across ethnicities [58–61]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [60]
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- Authors
- Jun, G. R., Chung, J., Mez, J., Barber, R., Beecham, G. W., Bennett, D. A., Buxbaum, J. D., Byrd, G. S., Carrasquillo, M. M., Crane, P. K., Cruchaga, C., De Jager, P., Ertekin‐Taner, N., Evans, D., Fallin, M. D., Foroud, T. M., Friedland, R. P., Goate, A. M., Graff‐Radford, N. R., Hendrie, H., Hall, K. S., Hamilton‐Nelson, K. L., Inzelberg, R., Kamboh, M. I., Kauwe, J. S. K., Kukull, W. A., Kunkle, B. W., Kuwano, R., Larson, E. B., Logue, M. W., Manly, J. J., Martin, E. R., Montine, T. J., Mukherjee, S., Naj, A., Reiman, E. M., Reitz, C., Sherva, R., St. George‐Hyslop, P. H., Thornton, T., Younkin, S. G., Vardarajan, B. N., Wang, L., Wendlund, J. R., Winslow, A. R., Adams, P. M., Albert, M. S., Albin, R. L., Apostolova, L. G., Arnold, S. E., Asthana, S., Atwood, C. S., Barmada, M. M., Barnes, L. L., Beach, T. G., Becker, J. T., Bigio, E. H., Bird, T. D., Blacker, D., Boeve, B. F., Bowen, J. D., Boxer, A., Burke, J. R., Cairns, N. J., Cao, C., Carlson, C. S., Carlsson, C. M., Carney, R. M., Carrasquillo, M. M., Carroll, S. L., Chui, H. C., Clark, D. G., Corneveaux, J., Cribbs, D. H., Crocco, E. A., Cruchaga, C., De Jager, P. L., DeCarli, C., DeKosky, S. T., Demirci, F. Y., Dick, M., Dickson, D. W., Doody, R. S., Duara, R., Ertekin‐Taner, N., Faber, K. M., Fairchild, T. J., Fallon, K. B., Farlow, M. R., Ferris, S., Frosch, M. P., Galasko, D. R., Gearing, M., Geschwind, D. H., Ghetti, B., Gilbert, J. R., Glass, J. D., Graff‐Radford, N. R., Green, R. C., Growdon, J. H., Hakonarson, H., Hamilton, R. L., Hardy, J., Harrell, L. E., Head, E., Honig, L. S., Huebinger, R. M., Huentelman, M. J., Hulette, C. M., Hyman, B. T., Jarvik, G. P., Jicha, G. A., Jin, L., Karydas, A., Kauwe, J. S. K., Kaye, J. A., Kim, R., Koo, E. H., Kowall, N. W., Kramer, J. H., LaFerla, F. M., Lah, J. J., Leverenz, J. B., Levey, A. I., Li, G., Lieberman, A. P., Lin, C., Lopez, O. L., Lyketsos, C. G., Mack, W. J., Marson, D. C., Martiniuk, F., Mash, D. C., Masliah, E., McCormick, W. C., McCurry, S. M., McDavid, A. N., McKee, A. C., Mesulam, M., Miller, B. L., Miller, C. A., Miller, J. W., Morris, J. C., Mukherjee, S., Murrell, J. R., Myers, A. J., O'Bryant, S., Olichney, J. M., Pankratz, V. S., Parisi, J. E., Partch, A., Paulson, H. L., Perry, W., Peskind, E., Petersen, R. C., Pierce, A., Poon, W. W., Potter, H., Quinn, J. F., Raj, A., Raskind, M., Reisberg, B., Reisch, J. S., Reitz, C., Ringman, J. M., Roberson, E. D., Rogaeva, E., Rosen, H. J., Rosenberg, R. N., Royall, D. R., Sager, M. A., Sano, M., Saykin, A. J., Schneider, J. A., Schneider, L. S., Seeley, W. W., Smith, A. G., Sonnen, J. A., Spina, S., Stern, R. A., Tanzi, R. E., Thornton‐Wells, T. A., Trojanowski, J. Q., Troncoso, J. C., Tsuang, D. W., Van Deerlin, V. M., Van Eldik, L. J., Vardarajan, B. N., Vinters, H. V., Vonsattel, J. P., Weintraub, S., Welsh‐Bohmer, K. A., Williamson, J., Wishnek, S., Woltjer, R. L., Wright, C. B., Wu, C., Yu, C., Yu, L., Zhang, X., Haines, J., Mayeux, R., Pericak‐Vance, M. A., Schellenberg, G., Lunetta, K. L., & Farrer, L. A.
- Affiliations
- Boston University (US)
- University of North Texas Health Science Center (US)
- University of Miami (US)
- Rush University Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
- North Carolina Agricultural and Technical State University (US)
- University of Washington (US)
- Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology & Psychiatry Brigham and Women's Hospital and Harvard Medical School Boston MA USA
- Johns Hopkins University (US)
- Indiana University Indianapolis (US)
- University of Louisville (US)
- Regenstrief Institute (US)
- Tel Aviv University (IL)
- University of Pittsburgh (US)
- Brain Research Institute, Niigata University (JP)
- Broad Institute (US)
- Columbia University Irving Medical Center (US)
- Stanford Medicine (US)
- University of Pennsylvania (US)
- Translational Genomics Research Institute (US)
- Tanz Centre for Research in Neurodegenerative Disease University of Toronto Toronto Canada
- Mayo Clinic (US)
- Arizona Alzheimer’s Consortium (US)
- Pfizer (United States) (US)
- Neurogenetics and Integrated Genomics Andover Innovative Medicines Institute, Eisai Inc Andover MA USA
- Case Western Reserve University (US)
- Corresponding author
- Farrer, Lindsay A.
- ORCID
- Jun, Gyungah R.
- Chung, Jaeyoon
- Mez, Jesse
- Barber, Robert
- Beecham, Gary W.
- Bennett, David A.
- Buxbaum, Joseph D.
- Byrd, Goldie S.
- Crane, Paul K.
- Evans, Denis
- Foroud, Tatiana M.
- Friedland, Robert P.
- Goate, Alison M.
- Hendrie, Hugh
- Hamilton‐Nelson, Kara L.
- Inzelberg, Rivka
- Kamboh, M. Ilyas
- Kukull, Walter A.
- Kunkle, Brian W.
- Larson, Eric B.
- Logue, Mark W.
- Manly, Jennifer J.
- Martin, Eden R.
- Montine, Thomas J.
- Naj, Adam
- Reiman, Eric M.
- Sherva, Richard
- Wang, Li‐San
- Winslow, Ashley R.
- Adams, Perrie M.
- Albert, Marilyn S.
- Albin, Roger L.
- Apostolova, Liana G.
- Arnold, Steven E.
- Asthana, Sanjay
- Atwood, Craig S.
- Barnes, Lisa L.
- Beach, Thomas G.
- Becker, James T.
- Bigio, Eileen H.
- Bird, Thomas D.
- Blacker, Deborah
- Boeve, Bradley F.
- Bowen, James D.
- Boxer, Adam
- Burke, James R.
- Cairns, Nigel J.
- Cao, Chuanhai
- Carlsson, Cynthia M.
- Carroll, Steven L.
- Chui, Helena C.
- Clark, David G.
- Cribbs, David H.
- Crocco, Elizabeth A.
- DeCarli, Charles
- DeKosky, Steven T.
- Demirci, F. Yesim
- Dickson, Dennis W.
- Duara, Ranjan
- Faber, Kelley M.
- Farlow, Martin R.
- Ferris, Steven
- Frosch, Matthew P.
- Galasko, Douglas R.
- Gearing, Marla
- Geschwind, Daniel H.
- Ghetti, Bernardino
- Gilbert, John R.
- Glass, Jonathan D.
- Green, Robert C.
- Hakonarson, Hakon
- Hamilton, Ronald L.
- Hardy, John
- Head, Elizabeth
- Honig, Lawrence S.
- Huebinger, Ryan M.
- Huentelman, Matthew J.
- Hyman, Bradley T.
- Jarvik, Gail P.
- Jicha, Gregory A.
- Kaye, Jeffrey A.
- Koo, Edward H.
- Kowall, Neil W.
- Kramer, Joel H.
- LaFerla, Frank M.
- Lah, James J.
- Leverenz, James B.
- Levey, Allan I.
- Lieberman, Andrew P.
- Lin, Chiao‐Feng
- Lyketsos, Constantine G.
- Mack, Wendy J.
- Marson, Daniel C.
- Martiniuk, Frank
- Mash, Deborah C.
- Masliah, Eliezer
- McCurry, Susan M.
- McDavid, Andrew N.
- McKee, Ann C.
- Mesulam, Marsel
- Miller, Bruce L.
- Morris, John C.
- Murrell, Jill R.
- Myers, Amanda J.
- Olichney, John M.
- Pankratz, Vernon S.
- Paulson, Henry L.
- Peskind, Elaine
- Petersen, Ronald C.
- Poon, Wayne W.
- Potter, Huntington
- Quinn, Joseph F.
- Raskind, Murray
- Reisberg, Barry
- Ringman, John M.
- Roberson, Erik D.
- Rogaeva, Ekaterina
- Sano, Mary
- Saykin, Andrew J.
- Schneider, Julie A.
- Schneider, Lon S.
- Seeley, William W.
- Smith, Amanda G.
- Sonnen, Joshua A.
- Spina, Salvatore
- Stern, Robert A.
- Tanzi, Rudolph E.
- Trojanowski, John Q.
- Troncoso, Juan C.
- Tsuang, Debby W.
- Vinters, Harry V.
- Williamson, Jennifer
- Woltjer, Randall L.
- Yu, Chang‐En
- Yu, Lei
- Zhang, Xiaoling
- Haines, Jonathan
- Mayeux, Richard
- Pericak‐Vance, Margaret A.
- Schellenberg, Gerard
- Lunetta, Kathryn L.
- Farrer, Lindsay A.
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2017-02-07
- Volume
- 13
- Issue
- 7
- Pages
- 727-738
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC5496797
- OpenAlex
- W2586698568
- Cited by
- 197
- References
- 9
- Citations by year
- 2026: 12 · 2025: 17 · 2024: 16 · 2023: 27 · 2022: 19 · 2021: 31 · 2020: 21 · 2019: 28 · 2018: 20 · 2017: 6
- FWCI
- 15.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG034504)
- National Association for Colitis and Crohn's Disease (U01 AG016976)
- Boston University (P30 AG013846, U01 AG10483, R01 CA129769, R01 MH080295, R01 AG017173, R01 AG33193, R01 AG048927)
- Columbia University (P50 AG008702, R37 AG015473)
- Duke University (P30 AG028377, AG05128)
- Emory University (AG025688)
- Indiana University (P30 AG10133)
- Johns Hopkins University (P50 AG005146, R01 AG020688)
- Massachusetts General Hospital (P50 AG005134)
- Mayo Clinic (P50 AG016574)
- New York University (P30 AG08051, MO1RR00096, UL1 RR029893)
- Northwestern University (P30 AG013854)
- Rush University (P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG30146)
- University of Alabama at Birmingham (P50 AG016582, UL1RR02777)
- University of Arizona (R01 AG031581)
- University of California, Davis (P30 AG010129)
- University of California, Irvine (P50 AG016573, P50, P50 AG016575, P50 AG016576, P50 AG016577)
- University of California, Los Angeles (P50 AG016570)
- University of California, San Diego (P50 AG005131)
- University of California, San Francisco (P50 AG023501, P01 AG019724)
- University of Kentucky (P30 AG028383)
- University of Michigan (P50 AG008671)
- University of Pennsylvania (P30 AG010124)
- University of Pittsburgh (P50 AG005133, AG030653)
- University of Southern California (P50 AG005142)
- University of Miami (R01 AG027944, AG010491, AG027944, AG021547, AG019757)
- University of Washington (P50 AG005136)
- Vanderbilt University (R01 AG019085)
- National Institute of Neurological Disorders and Stroke (#NS39764, NIMH MH60451)
- GlaxoSmithKline
- Banner Alzheimer’s Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, late-onset Alzheimer's disease
- MeSH terms
- Alzheimer Disease, Humans, Membrane Glycoproteins, Receptors, GABA, Molecular Chaperones, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, GTPase-Activating Proteins, Adaptor Proteins, Signal Transducing, NFI Transcription Factors, Apolipoprotein E4, Genome-Wide Association Study, Peroxisomal Bifunctional Enzyme, Heparin-binding EGF-like Growth Factor
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