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

Authors: Gyungah Jun, Jaeyoon Chung, Jesse Mez, Robert C. Barber, Gary W. Beecham, David A. Bennett, Joseph D. Buxbaum, Goldie S. Byrd, Minerva M. Carrasquillo, Paul K. Crane, Carlos Cruchaga, Philip L. De Jager, Nilüfer Ertekin‐Taner, Denis A. Evans, M. Danielle Fallin, Tatiana Foroud, Robert P. Friedland, Alison Goate, Neill R. Graff‐Radford, Hugh C. Hendrie, Kathleen 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 C. Naj, Eric M. Reiman, Christiane Reitz, Richard Sherva, Peter St George‐Hyslop, Timothy Thornton, Steven G. Younkin, Badri N. Vardarajan, Li‐San Wang, Jens R. Wendlund, Ashley R. Winslow, Perrie M. Adams, Marilyn S. Albert, Roger L. Albin, Liana G. Apostolova, Steven E. Arnold, Sanjay Asthana, Craig Atwood, Michjael M Barmada, Lisa L. Barnes, Thomas G. Beach, James T. Becker, Eileen H. Bigio, Thomas D. Bird, Deborah Blacker, Bradley F. Boeve, James D. Bowen, Adam Boxer, James R. Burke, Nigel J. Cairns, Chuanhai Cao, Chris Carlson, Cynthia M. Carlsson, Regina M. Carney, Minerva M. Carrasquillo, Steven L. Carroll, Helena C. Chui, David G. Clark, Jason J. Corneveaux, David H. Cribbs, Elizabeth Crocco, Carlos Cruchaga, Philip L. De Jager, Charles DeCarli, Steven T. DeKosky, F. Yesim Demirci, Malcolm Dick, Dennis W. Dickson, Rachelle S. Doody, Ranjan Duara, Nilüfer Ertekin‐Taner, Kelley Faber, Thomas Fairchild, Kenneth B. Fallon, Martin R. Farlow, Steven H. Ferris, Matthew P. Frosch, Douglas Galasko, Marla Gearing, Daniel H. Geschwind, Bernardino Ghetti, John R. Gilbert, Jonathan D. Glass, Neill R. Graff‐Radford, Robert C. Green, John H. Growdon, Håkon Håkonarson, Ronald L. Hamilton, John Hardy, Lindy E. Harrell, Elizabeth Head, Lawrence S. Honig, Ryan Huebinger, Matthew J. Huentelman, Christine M. Hulette, Bradley T. Hyman, Gail P. Jarvik, Gregory A. Jicha, Lee‐Way Jin, Anna Karydas, John S. K. Kauwe, Jeffrey Kaye, Ronald Kim, Edward H. Koo, Neil W. Kowall, Joel H. Kramer, Frank M. LaFerla, James J. Lah, James B. Leverenz, Allan I. Levey, Li Ge, Andrew P. Lieberman, Chiao‐Feng Lin, Oscar L. López, Constantine G. Lyketsos, Wendy J. Mack, Daniel Marson, Frank Martiniuk, Deborah C. Mash, Eliezer Masliah, Wayne C. McCormick, Susan M. McCurry, Andrew McDavid, Ann C. McKee, Marsel Mesulam, Bruce L. Miller, Carol A. Miller, Joshua W. Miller, John C. Morris, Shubhabrata Mukherjee, Jill R. Murrell, Amanda Myers, Sid E. O’Bryant, John Olichney, V. Shane Pankratz, Joseph E. Parisi, Amanda Partch, Henry L. Paulson, William Perry, Elaine R. Peskind, Ronald Petersen, Aimee Pierce, Wayne W. Poon, Huntington Potter, Joseph F. Quinn, Ashok Raj, Murray A. Raskind, ‌Barry Reisberg, Joan Reisch, Christiane Reitz, John M. Ringman, Erik D. Roberson, Ekaterina Rogaeva, Howard J. Rosen, Roger N. Rosenberg, Donald R. Royall, Mark A. Sager, Mary Sano, Andrew J. Saykin, Julie A. Schneider, Lon S. Schneider, William W. Seeley, Amanda Smith, Joshua A. Sonnen, Salvatore Spina, Robert A. Stern, Rudolph E. Tanzi, Tricia A. Thornton‐Wells, John Q. Trojanowski, Juan C. Troncoso, Debby W. Tsuang, Vivianna M. Van Deerlin, Linda J. Van Eldik, Badri N. Vardarajan, Harry V. Vinters, Jean Paul Vonsattel, Sandra Weıntraub, Kathleen A. Welsh‐Bohmer, Jennifer Williamson, Sarah Wishnek, Randall L. Woltjer, Clinton B. Wright, Chuang‐Kuo Wu, Chang‐En Yu, Lei Yu, Xiaoling Zhang, Jonathan L. Haines, Richard Mayeux, Margaret A. Pericak‐Vance, Gerard Schellenberg, Kathryn L. Lunetta, Lindsay A. Farrer - Alzheimer s & Dementia 2017 cited by 210

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.