S4‐01‐04: CSF Ad Biomarkers and Amyloid Pet Imaging Provide us with Similar Information in Prodromal Alzheimer’s Disease

not available. WEDNESDAY, JULY 27, 2016 SYMPOSIA S4-02 ADVANCES IN GENETIC STUDIES S4-02-01 ALZHEIMER’S DISEASE SEQUENCING PROJECT: CASE-CONTROL ANALYSES Adam C. Naj and the Alzheimer’s Disease Sequencing Project, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Contact e-mail: adamnaj@mail.med.upenn.edu Background:Responding to a 2012Presidential Initiative to fightAlzheimer’s disease (AD), theNational InstituteonAging (NIA) andNational Human Genome Research Institute (NHGRI) jointly developed a project to analyze the genomes of a large number of well-characterized individuals with or without AD using $25M in funding already committed to the NHGRI’s Large-scale Sequencing and Analysis Centers. The overarching goals of this effort, the Alzheimer’s Disease Sequencing Project (ADSP), include identifying new (1) genes involved in AD, (2) genomic variation contributing to AD risk or protection, and (3) potential avenues (“druggable targets”) for therapies and AD prevention. This presentation highlights the work done in the ADSP Discovery Phase Case-Control Study, examining genotypic associations in whole exome sequence (WES) data fromw10,500unrelated participants taken from theAlzheimer’s Disease Genetics Consortium (ADGC) and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Methods:We selected 5,107 cases and 4,976 controls on the basis of age, sex,APOEgenotype, andpathology, and to enrich the risk profile and diversity of the study, unrelated cases from AD families (N1⁄4512) as well as Dominican-Hispanic cases (N1⁄4173) and controls (N1⁄4171) were also sequenced. Association analyses performed on these data have included (a) multivariate logistic regression of individual common variants (minor allele count (MAC)> 10); (b) Score tests and Firth bias-corrected regression for rare, functional variants (MAC 10); and (c) gene-based association using burden tests andSKAT to examine rare functional variants, with specific subsetting for loss-of-function (LOF) variants. Approximately 1.6 million SNVs and 50,000 indels passing quality control were analyzed using SeqMeta/R, with covariate adjustment for age, sex, and population substructure; statistical significance was established using a Bonferroni correction. Results: Single variant associations identified common and rare variant associations in several known AD risk genes (APOE, TREM2, and ABCA7), while gene-based tests of LOF variants identified two novel gene associations in OPRL1 and GAS2L2. Indel associations are on-going and will be updated; results of these analyses will be presented. Conclusions: WES association analyses of ADSP case-control data replicated several known AD genes and identified two novel associations; replication of these associations is currently underway. S4-02-02 ALZHEIMER’S DISEASE SEQUENCING PROJECT: FAMILY-BASED ANALYSES Ellen Wijsman, University of Washington, Seattle, WA, USA. Contact e-mail: wijsman@u.washington.edu Abstract not available.not available. S4-02-03 ACCELERATING MEDICINES PARTNERSHIP: CO-EXPRESSION NETWORKS Minghui Wang, Panos Roussos, Andrew McKenzie, Pavel Katsel, Patrizia Casaccia, Eric Schadt, Vahram Haroutunian, Bin Zhang, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Contact e-mail: bin.