Alzheimer's Disease Sequencing Project. Homo sapiens

On February 7, 2012, a Presidential Initiative was announced for Alzheimer’s Disease (AD) to analyze the genomes of a large number of well characterized individuals in order to identify a broad range of AD risk and protective gene variants. The ultimate goal is to facilitate the identification of new pathways for therapeutic approaches and prevention. The analysis will also provide insight as to why individuals with known risk factor genes escape from developing AD. The effort is called the Alzheimer’s Disease Sequencing Project (ADSP); there are four components to the ADSP. Family-Based sequencing: whole genome sequencing (WGS) of 582 family members from 111 informative multiplex families to identify genomic regions associated with increased risk of AD. Case-Control sequencing: whole exome capture sequencing (WES) of 5,000 cases / 5,000 controls for both risk raising and protective loci. Enriched Case sequencing: in addition to the cases above, WES from an additional case group made-up of one individual from 1,000 additional AD families to identify regions associated with increased risk or protection from AD. Replication and Validation of regions identified from case-control and family sequencing in a large number of samples from well phenotyped individuals by targeted sequencing and/or genotyping. 50,000 samples are targeted, but the final number may be smaller. Deep targeted sequencing of candidate AD regions identified by previous linkage and chip-based association (GWAS and exome chip) and ADSP sequenced-based, analyses will identify potential functional variants beyond the exomes in regions implicated in and validated for AD risk and protection. Sequencing for this project is being carried out by three NHGRI-funded Large Scale Sequencing and Analysis Centers: the Human Genome Sequencing Center at the Baylor College of Medicine, the Broad Institute Genome Center, and the Washington University Genome Institute. The samples for the ADSP are selected from well-characterized, cohorts of individuals characterized for AD diagnosis as well as having known AD genetic risk factors. Sample selection was agreed upon by the ADSP Steering Committee. For the Family-Based, Case-Control, and the Enriched Case studies, samples were provided by the two consortia: the Alzheimer’s Disease Genetics Consortium (ADGC) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Samples for the Replication and Validation will be provided by collaborators within the US as well as internationally. Data from the ADSP can be found via links to the NIA Genetics of Alzheimer’s Disease Data Storage Site (https://www.niagads.org/) and dbGaP (http://www.ncbi.nlm.nih.gov/gap).