Adam C Naj1,115, Gyungah Jun2-4,115, Gary W Beecham1,5, Li-San Wang6, Badri Narayan Vardarajan3, Jacqueline Buros3, Paul J Gallins1, Joseph D Buxbaum7-9, Gail P Jarvik10,11, Paul K Crane12, Eric B Larson13, Thomas Bird14, Bradley F Boeve15, Neill R Graff-Radford16,17, Philip L De Jager18,19, Denis Evans20, Julie A Schneider21,22, Minerva M Carrasquillo16, Nilufer Ertekin-Taner16,17, Steven G Younkin16, Carlos Cruchaga23, John S Kauwe24, Petra Nowotny23, ..et al.
1The John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA. 2Department of Biostatistics, Boston University, Boston, Massachusetts, USA. 3Department of Medicine (Genetics Program), Boston University, Boston, Massachusetts, USA. 4Department of Ophthalmology, Boston University, Boston, Massachusetts, USA. 5Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miami, Florida, USA. 6Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA. 7Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, USA. 8Department of Psychiatry, Mount Sinai School of Medicine, New York, New York, USA. 9Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, USA. 10Department of Genome Sciences, University of Washington, Seattle, Washington, USA. 11Department of Medicine (Medical Genetics), University of Washington, Seattle, Washington, USA. ...115These authors contributed equally to this work. Correspondence should be addressed to G.D.S..
*A full list of authors and affiliations appears at the end of the paper.
The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (PM) = 1.7 × 10-9, joint analysis P (PJ) = 1.7× 10-9; stages 1, 2 and 3, PM = 8.2 × 10-12), CD2AP (rs9349407; stages 2 and 3, PM = 8.6 × 10-9), EPHA1 (rs11767557; stages 2 and 3, PM = 6.0 × 10-10) and CD33 (rs3865444; stages 2 and 3, PM = 1.6 × 10-9). We also replicated previous associations at CR1 (rs6701713; PM = 4.6 × 10-10, PJ = 5.2 × 10-11), CLU (rs1532278; PM = 8.3 ×10-8, PJ = 1.9 × 10-8), BIN1 (rs7561528; PM = 4.0 × 10-14, PJ = 5.2 × 10-14) and PICALM (rs561655; PM = 7.0 × 10-11, PJ = 1.0 × 10-10), but not at EXOC3L2, to late-onset Alzheimer’s disease susceptibility1-3.