NACC's partnerships in genetics and imaging | National Alzheimer's Coordinating Center

NACC partnerships

NACC + NCRAD + NIAGADS + ADGC = A rich data source

  • The National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD) provides biological samples.
  • The NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS) provides genetic data to any qualified researcher.
  • The Alzheimer’s Disease Genetics Consortium (ADGC) also provides genetic data, but only to the ADRCs.
  • NACC provides longitudinal clinical data on almost 40,000 participants in its Uniform Data Set (2005-present), and neuropathologic data on a subset of these. In addition, the Minimum Data Set (MDS), offers abstracted data on ADRC subjects from 1984 to 2005. A large number of these also have neuropathology data.

NACC, NCRAD, NIAGADS, and the Alzheimer’s Disease Research Centers (ADRCs) work together to track phenotypic data, biologic specimens, and genotypic data from ADRC participants. Researchers can request data or specimens from the relevant NIA-supported resource. Often, multiple types of data are available for the same participants — in which case, participant identifiers can be used to tie the various available data together.

NACC, a resource for longitudinal participant data

For more information about NACC’s large relational database of standardized clinical and neuropathological research data, check out a summary of the NACC database, query system, or the UDS Researcher’s Data Dictionary. A NACC data request can take the form of a Quick-access Full Data File or a custom data set tailored to your research question.

NCRAD, a resource for biological samples

NCRAD’s catalogs of biospecimens include a limited data set from the NACC Uniform Data Set (UDS). In addition, the catalogs provide links to NIAGADS datasets for subjects with available genetic data.

  • NCRAD is the NIA-designated biorepository for biospecimens from dementia-related studies
  • It banks a broad range of samples that can be requested by qualified investigators. These include DNA, RNA, plasma, serum, CSF, brain tissue, lymphoblastoid cell lines (LCLs), peripheral blood mononuclear cells (PBMCs), induced pluripotent stem cells (iPSCs), fibroblasts, and feces.

ADGC, a resource for ADRC genetic data

The goal of the ADGC is to identify genetic variants associated with risk for AD. It has long been known that genetic factors play an important role in the development of AD. Researchers affiliated with an ADRC may request genetic data from ADGC from any Center including their own.

Genetic and genomic data

Genotypic data

NACC works in close collaboration with the Alzheimer's Disease Research Centers (ADRCs), the National Centralized Repository for Alzheimer's Disease and Related Disorders (NCRAD) , the Alzheimer's Disease Genetics Consortium (ADGC) , and the NIA Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) to advance GWAS efforts in Alzheimer's disease.

NACC, NCRAD, and the ADRCs work together to track GWAS subjects and any DNA, blood, buffy coat, or brain tissue samples sent for genotyping. NACC shares limited phenotype data with ADGC and serves as a data repository from which each ADRC may access its own genotype data.

Researchers wishing to gain access to comprehensive ADGC data must submit a proposal directly to ADGC or NIAGADS. For more information on requesting data from NIAGADS and the ADGC, see this description provided by NIAGADS. For subjects in ADRC studies, common IDs permit the GWAS data sets housed at ADGC and NIAGADS to be easily linked to UDS, NP, and MRI data from NACC.

To help researchers obtain ADGC data, NACC can provide a sample-size estimate of subjects meeting your eligibility criteria who also have genotype data available at ADGC:

  1. Provide NACC with your eligibility criteria, and we can produce a sample-size table and/or a list of the subjects that meet your criteria and that have genetic data at ADGC or NIAGADS. You can request clinical data for these subjects at that time, if desired.
  2. Use the list of subjects provided by NACC to further narrow your sample of interest, and then contact ADGC or NIAGADS to obtain genetic data.
  3. If you have already been approved to obtain genetic data from ADGC or NIAGADS and would like to request phenotypic data from NACC, please submit a data request and provide NACC with the list of NACCIDs.

Genomic data

HRC imputed values

Genotypes were imputed to the Haplotype Reference Consortium (HRC) reference panel of 64,976 haplotypes at 39,235,157 SNPs across the genome, all with an estimated minor allele count ≥5. The HRC utilizes genotypes from 20 different studies with low-coverage whole-genome sequencing data (4–8X coverage) on samples with predominantly European ancestry; however, the ethnically diverse 1000 Genomes Project Phase 3 cohort is also included. These sequence genotypes were phased and developed into a haplotype reference panel available for download through dbGaP, or for online imputation through a server managed by the University of Michigan.

GWAS genotypes were uploaded to the secure Michigan Imputation Server imputed to the HRC reference panel using the Minimac3 program, and the imputed genotype probabilities were subsequently downloaded for analyses. A detailed description of the HRC reference panel can be found in Nature Genetics (McCarthy et al., “A reference panel of 64,976 haplotypes for genotype imputation” Nat Genet 2016; 48 (10): 1279-83 [PMID: 27548312]).

1000 Genome imputed values

Genome-wide imputation of allele dosages was performed on samples passing quality control using the March 2012 panel from the 1000 Genomes build 37 for imputation of genotypes and the IMPUTE2 software applying strict prephasing, preimputation filtering, and variant position and strand alignment control.

The file types provided (.gen and .sample) can be directly used by SNPTEST for analysis. For an additional description of the file types, see the GTOOL documentation. In addition, GTOOL can be used to convert these data into PED/MAP format used by PLINK.

NIAGADS, a resource for participant genetic data

NIAGADS is a national genetics data repository that facilitates access to data by qualified investigators. It archives, processes, and distributes data related to the genetics and genomics of Alzheimer’s disease. With NIAGAD’s tools, researchers can examine and compare the genomes of individuals with and without cognitive impairment.

Data available from NIAGADS and its partner sites include genomic data from NIA-funded genetic studies, deep phenotype data and biomarkers, primary and secondary analyses including CHIP-Seq, RNA-Seq, and expression data, genome-wide association studies, and more.

Using these resources together

There are many ways to combine these resources. For example, after receiving longitudinal data from NACC, a participant’s NACC ID can be provided to NCRAD to receive any biological specimens available for that individual. The same NACC ID can then be provided to NIAGADS to receive any genomic data available for the participant.

Making your data requests

NACC: Once you have familiarized yourself with the data available through NACC, you simply accept our data use agreement and submit a data request.

NCRAD: To see what ADRC samples are available at NCRAD, please visit NCRAD’s section on accessing data and look for the ADRC cohort. Completing the NCRAD data agreement provides a login for access to the online catalog. The catalog includes a limited set of data from NACC, along with specimen information to help you select samples that best fit your research needs. Inclusion of the NACC ID allows data requested from NACC and NIAGADS to be linked to the NCRAD ADRC catalog.

ADGC: ADRC researchers should contact ADGC directly for access to the genotype and sequencing data.

NIAGADS: Browse the data available at NIAGADS, and then create an account and submit yourrequest.