Alzheimer's Disease Sequencing Project (ADSP)

The overarching goals of the ADSP are to: (1) identify new genomic variants contributing to increased risk of developing AD, (2) identify new genomic variants contributing to protection against developing AD, and (3) provide insight as to why individuals with known risk factor variants escape from developing AD. Such a study of human genomic variation and its relationship to health and disease requires examination of a large number of study participants and needs to capture information about common and rare variants (both single nucleotide and copy number). Using existing samples from NIH funded and other studies, the NHGRI LSSC will produce the DNA sequence data and generate variant calls that will be made available to the scientific community through NIH-approved data repositories. Statistical analysis of the sequence data is anticipated to identify new genetic risk and protective factors. Both fundamental scientific discovery and leading edge analytic approaches will be needed to achieve the research goals. The ADSP will conduct and facilitate analysis of sequence data to extend previous discoveries that may ultimately result in new directions for AD therapeutics.

The specific aims of the ADSP are to: (1) identify protective genomic variants in older adults at risk for AD, (2) identify new risk variants among AD cases, and (3) examine these factors in multi-ethnic populations as applicable in order to identify new pathways for disease prevention.

For more information, please visit https://www.niagads.org/adsp/.

• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
  • Family
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 4708
• Subject Sample Telemetry Report (SSTR)

The samples for the ADSP have been selected from well-characterized cohorts of individuals characterized for AD diagnosis as well as having known AD genetic risk factors. Investigators in the ADSP will obtain from the NIH approved data repositories: (1) quality control checked and 'cleaned' sequence data. 'Quality control checked and cleaned' means a set of routine checks have been performed for sample information, phenotype, and GWAS data to ensure the sequence data are of high quality and are ready for downstream genetic analysis and that likely sources of false-positives have been ruled out, and that samples that are outliers which may skew project-level analyses have been identified; (2) information on the composition of the study cohorts (e.g. case-control, family based, and epidemiology cohorts); (3) descriptions of the study cohorts included in the study; and (4) accompanying phenotypic information such as age at disease onset, self-reported race/ethnicity, gender, diagnostic status, and cognitive measures. The ADSP will determine what additional information, if any, is needed by its members to facilitate the project.

On February 7, 2012, a new Presidential Initiative was announced to fight Alzheimer's Disease (AD). As part of this effort, the National Human Genome Research Institute (NHGRI) was asked by the Director of the National Institutes of Health (NIH) to use $25M already committed to its Large-Scale Sequencing Centers (LSSC) for genomic studies in AD. The NIH director asked the National Institute on Aging (NIA) and the NHGRI to work together to develop and execute a large scale sequencing project 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, with the ultimate goal of facilitating 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 project, developed jointly by NIA and NHGRI, is called the Alzheimer's Disease Sequencing Project (ADSP).

• Primary Phenotype: Alzheimer Disease

• Principal Investigators
  • Richard A. Gibbs, PhD. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
  • Eric S. Lander, PhD. Broad Institute, Boston, MA, USA.
  • Richard K. Wilson, PhD. The Genome Institute, Washington University, St. Louis, MO, USA.
  • Gerard D. Schellenberg, PhD. Alzheimer's Disease Genetics Consortium (ADGC), University of Pennsylvania, Philadelphia, PA, USA.
  • Sudha Seshadri, MD. Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Boston University, Boston, MA, USA.
• Funding Sources
  • U24 AG041689. The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.
  • U01 AG032984. Alzheimer's Disease Genetics Consortium, University of Pennsylvania, Philadelphia, PA, USA.
  • R01 AG033193. Cohorts for Heart and Aging Research in Genomic Epidemiology, Boston University, Boston, MA, USA.
  • U24 AG021886. National Cell Repository for Alzheimer's Disease, Indiana University, Bloomington, IN, USA.
• Funding Sources for Sequencing
  • U54HG003079. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • U54HG003273. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • U54HG003076. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.