Transethnic genome‐wide scan identifies novel Alzheimer's disease loci
Authors: Jun Gyungah R. , Chung Jaeyoon , Mez Jesse , Barber Robert , Beecham Gary W. , Bennett David A. , Buxbaum Joseph D. , Byrd Goldie S. , Carrasquillo Minerva M. , Crane Paul K. , Cruchaga Carlos , De Jager Philip , 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. , Adams Perrie M. , Albert Marilyn S. , Albin Roger L. , Apostolova Liana G. , Arnold Steven E. , Asthana Sanjay , Atwood Craig S. , Barmada Michjael M. , 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 , Carlson Chris S. , Carlsson Cynthia M. , Carney Regina M. , Carrasquillo Minerva M. , Carroll Steven L. , Chui Helena C. , Clark David G. , Corneveaux Jason , Cribbs David H. , Crocco Elizabeth A. , Cruchaga Carlos , De Jager Philip L. , DeCarli Charles , DeKosky Steven T. , Demirci F. Yesim , Dick Malcolm , Dickson Dennis W. , Doody Rachelle S. , Duara Ranjan , Ertekin‐Taner Nilufer , Faber Kelley M. , Fairchild Thomas J. , Fallon Kenneth B. , Farlow Martin R. , Ferris Steven , Frosch Matthew P. , Galasko Douglas R. , Gearing Marla , Geschwind Daniel H. , Ghetti Bernardino , Gilbert John R. , Glass Jonathan D. , Graff‐Radford Neill R. , Green Robert C. , Growdon John H. , Hakonarson Hakon , Hamilton Ronald L. , Hardy John , Harrell Lindy E. , Head Elizabeth , Honig Lawrence S. , Huebinger Ryan M. , Huentelman Matthew J. , Hulette Christine M. , Hyman Bradley T. , Jarvik Gail P. , Jicha Gregory A. , Jin Lee‐Way , Karydas Anna , Kauwe John S.K. , Kaye Jeffrey A. , Kim Ronald , Koo Edward H. , Kowall Neil W. , Kramer Joel H. , LaFerla Frank M. , Lah James J. , Leverenz James B. , Levey Allan I. , Li Ge , Lieberman Andrew P. , Lin Chiao‐Feng , Lopez Oscar L. , Lyketsos Constantine G. , Mack Wendy J. , Marson Daniel C. , Martiniuk Frank , Mash Deborah C. , Masliah Eliezer , McCormick Wayne C. , McCurry Susan M. , McDavid Andrew N. , McKee Ann C. , Mesulam Marsel , Miller Bruce L. , Miller Carol A. , Miller Joshua W. , Morris John C. , Mukherjee Shubhabrata , Murrell Jill R. , Myers Amanda J. , O'Bryant Sid , Olichney John M. , Pankratz Vernon S. , Parisi Joseph E. , Partch Amanda , Paulson Henry L. , Perry William , Peskind Elaine , Petersen Ronald C. , Pierce Aimee , Poon Wayne W. , Potter Huntington , Quinn Joseph F. , Raj Ashok , Raskind Murray , Reisberg Barry , Reisch Joan S. , Reitz Christiane , Ringman John M. , Roberson Erik D. , Rogaeva Ekaterina , Rosen Howard J. , Rosenberg Roger N. , Royall Donald R. , Sager Mark A. , 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. , Thornton‐Wells Tricia A. , Trojanowski John Q. , Troncoso Juan C. , Tsuang Debby W. , Van Deerlin Vivianna M. , Van Eldik Linda J. , Vardarajan Badri N. , Vinters Harry V. , Vonsattel Jean Paul , Weintraub Sandra , Welsh‐Bohmer Kathleen A. , Williamson Jennifer , Wishnek Sarah , Woltjer Randall L. , Wright Clinton B. , Wu Chuang‐Kuo , Yu Chang‐En , Yu Lei , Zhang Xiaoling , Haines Jonathan , Mayeux Richard , Pericak‐Vance Margaret A. , Schellenberg Gerard , Lunetta Kathryn L. , Farrer Lindsay A. 
Published: February 2017

AbstractIntroductionGenetic 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.MethodsWe 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.ResultsGenome‐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).DiscussionOur findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.