Gyungah R. Jun^a,b, Jaeyoon Chung^b, Jesse Mez^c, Robert Barber^d, Gary W. Beecham^e, David A. Bennett^f, Joseph D. Buxbaum^g,h,i, Goldie S. Byrd^j, Minerva M. Carrasquillo^k, Paul K. Crane^l, Carlos Cruchaga^m,n, Philip De Jager^o,p, Nilufer Ertekin-Taner^k, Denis Evans^q, M. Danielle Fallin^r, Tatiana M. Foroud^s, Robert P. Friedland^t, Alison M. Goate^g, Neill R. Graff-Radford^k, Hugh Hendrie^u,v, Kathleen S. Hall^v,w, Kara L. Hamilton-Nelson^e, Rivka Inzelberg^x, M. Ilyas Kamboh^y, John S. K. Kauwez,Walter A. Kukull^aa,bb, BrianW. Kunkle^e, Ryozo Kuwano^cc, Eric B. Larson^p,dd, MarkW. Logue^b,f,ee, Jennifer J. Manly^ff,gg, Eden R. Martin^e, Thomas J. Montine^hh, Shubhabrata Mukherjee^l, Adam Najⁱⁱ, Eric M. Reiman^jj,kk,ll,mm, Christiane Reitz^nn,oo,pp, Richard Sherva^b, Peter H. St. George-Hyslop^qq,rr, Timothy Thornton^l, Steven G. Younkin^k, Badri N. Vardarajan^ff,gg,nn, Li-San Wang^jj, Jens R. Wendlund^ss, Ashley R. Winslow^ss, Alzheimer’s Disease Genetics Consortiu^m, Jonathan Haines^tt, Richard Mayeux^{ff,gg,nn,oo,pp}, Margaret A. Pericak-Vanc^ee, Gerard Schellenberg^jj, Kathryn L. Lunetta^uu, Lindsay A. Farrer<sup>b,c,uu,vv,ww,*

a</sup> Andover Innovative Medicines Institute, Eisai Inc, Andover, MA, USA
^bDepartment of Medicine (Biomedical Genetics), Boston University Schools of Medicine and Public Health, Boston, MA, USA
^cDepartment of Neurology, Boston University Schools of Medicine and Public Health, Boston, MA, USA
^dDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, TX, USA
^eThe John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA
^fDepartment of Neurological Sciences and Rush Alzheimer’s Disease Center, Chicago, IL, USA
^gDepartment of Neuroscience, Mount Sinai School of Medicine, New York, NY, USA
^hDepartment of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA
ⁱDepartment of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, NY, USA
^jDepartment of Biology, North Carolina A&T State University, Greensboro, NC, USA
^kDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA
^lDepartment of Medicine, University of Washington, Seattle, WA, USA
^mHope Center Program on Protein Aggregation and Neurodegeneration, Washington University School of Medicine, St Louis, MO, USA
ⁿDepartment of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
^oProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Department of Neurology & Psychiatry, Brigham and Women’s
^Hospital and Harvard Medical School, Boston, MA, USA
^pProgram in Medical and Population Genetics, Broad Institute, Cambridge, MA, USA
^qRush Institute for Healthy Aging, Department of Internal Medicine, Rush University Medical Center, Chicago, IL, USA
^rDepartment of Mental Health, Johns Hopkins University School of Medicine, Baltimore, MD, USA
^sDepartment of Medical & Molecular Genetics, Indiana University, Indianapolis, IN, USA
^tDepartment of Neurology, University of Louisville, Louisville, KY, USA
^uDepartment of Psychiatry, Indiana University, Indianapolis, IN, USA
^vRegenstrief Institute, Inc, Indianapolis, IN, USA
^wDepartment of Medicine, Indiana University, Indianapolis, IN, USA
^xDepartment of Neurology and Neurosurgery, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
^yUniversity of Pittsburgh Alzheimer’s Disease Research Center and Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
^zDepartment of Biology, Brigham Young University, Provo, UT, USA
^aaDepartment of Epidemiology, University of Washington, Seattle, WA, USA
^bbNational Alzheimer’s Coordinating Center, University of Washington, Seattle, WA, USA
^ccDepartment of Molecular Genetics, Brain Research Institute, Niigata University, Niigata, Japan
^ddGroup Health, Group Health Research Institute, Seattle, WA, USA
^eeNational Center for PTSD, Behavioral Science Division, Boston VA Healthcare System, Boston, MA, USA
^ffThe Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY, USA
^ggThe Gertrude H. Sergievsky Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA
^hhDepartment of Pathology, Stanford University, Stanford, CA, USA
ⁱⁱDepartment of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA
^jjArizona Alzheimer’s Consortium, Phoenix, AZ, USA
^kkDepartment of Psychiatry, University of Arizona, Phoenix, AZ, USA
^llBanner Alzheimer’s Institute, Phoenix, AZ, USA
^mmNeurogenomics Division, Translational Genomics Research Institute, Phoenix, AZ, USA
ⁿⁿThe Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
^ooThe Department of Psychiatry, College of Physicians and Surgeons, Columbia University, New York, NY, USA
^ppThe Department of Epidemiology, College of Physicians and Surgeons, Columbia University, New York, NY, USA
^qqTanz Centre for Research in Neurodegenerative Disease, University of Toronto, Toronto, Canada
^rrCambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK
^ssPharmaTherapeutics Clinical Research, Pfizer Worldwide Research and Development, Cambridge, MA, USA
^ttDepartment of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA
^uuDepartment of Biostatistics, Boston University Schools of Medicine and Public Health, Boston, MA, USA
^vvDepartment of Ophthalmology, Boston University Schools of Medicine and Public Health, Boston, MA, USA
^wwDepartment of Epidemiology, Boston University Schools of Medicine and Public Health, Boston, MA, USA

^*Corresponding author

Abstract
Background: 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 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 5 1.8×10^-6).

Discussion: Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

Keywords: Transethnic; Alzheimer’s disease; Genome-wide association; APOE interaction