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:
- 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.
- 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.
- 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.
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.