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

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.