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ADSP Data Analysis

PI
Schellenberg, Gerard
DAR ID
10001
Initial Approval Date
August 23, 2018
Current DAR Status
Active
PI Institution
University of Pennsylvania
PI Institution Country
United States
PI Institution Type
Non-Profit

Requested Datasets (1)

NG00067Alzheimer's Disease Sequencing Project Umbrella Study

Research Use Statement
As part of the Consortium for Alzheimers Sequence Analysis (CASA: NIA grant U19AG047133). We plan to analyze whole exome and whole genome sequence data generated from subjects with Alzheimer's disease (AD) and elderly normal controls. These data will be generated by the National Human Genome Institute Large-Scale Sequence Program. The goal of the planned analyses is to identify genes that have alleles that protect against or increase susceptibility to AD. We will evaluate variants detected in the sequence data for association with AD to identify protective and susceptibility alleles using the whole exome and whole genome case-control data. We will also evaluate sequence data from multiplex AD families to identify variants associated with AD risk and protection, and evaluate variant co-segregation with AD. The family data will be whole genome data. The family-based data will be used to inform the cases control analysis and visa veras. We also will focus on structural variants (insertion-deletions, copy number variants, and chromosomal rearrangements). Evaluation of structural variants will involve both whole genome and whole exome data. Structural variants will be analyzed with single nucelotide variants detected and analyzed in the case-control and family-based data.

Non-Technical Summary
We are attempting to identify all the inherited elements that contribute to Alzheimer's disease risk. To do this we will analyze DNA sequence data from subjects with Alzheimer's disease and elderly subjects who are cognitively normal. The sequence data from these 2 groups will be compared to identify differences that contribute to the risk of developing Alzheimer's disease of that protect against Alzheimer's disease. These DNA differences can be at a single site in the genetic code, or can span multiple sites, changing the copy number of DNA sequences. Both types of genetic variants will be examined.

Reported Publications (35)

Publications shown are those reported by investigators through NIAGADS DAR reporting and renewal processes and may not represent a complete list of publications associated with the project.

  1. Alzheimer's Disease Sequencing Project release 4 whole genome sequencing dataset. Leung YY, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. PMID: 40407102
  2. Copy Number Variation and Haplotype Analysis of 17q21.31 Reveals Increased Risk Associated with Progressive Supranuclear Palsy and Gene Expression Changes in Neuronal Cells. Wang H, et al. Movement disorders : official journal of the Movement Disorder Society. 2025. PMID: 40055946
  3. Evaluating the association of APOE genotype and cognitive resilience in SuperAgers. Durant A, et al. medRxiv : the preprint server for health sciences. 2025. PMID: 39830268
  4. Multi-ancestry meta-analysis identifies genetic modifiers of age-at-onset of Alzheimer's disease at known and novel loci. Blue EE, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. PMID: 40883957
  5. Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease. Guo MH, et al. Nature communications. 2025. PMID: 39875385
  6. Structural variation detection and association analysis of whole-genome-sequence data from 16,543 Alzheimer's disease sequencing project subjects. Wang H, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. PMID: 40528303
  7. A comparative study of structural variant calling in WGS from Alzheimer's disease families. Malamon JS, et al. Life science alliance. 2024. PMID: 38418088
  8. Association of common and rare variants with Alzheimer's disease in more than 13,000 diverse individuals with whole-genome sequencing from the Alzheimer's Disease Sequencing Project. Lee WP, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 39428839
  9. Longitudinal change in memory performance as a strong endophenotype for Alzheimer's disease. Archer DB, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 37985223
  10. NIAGADS Alzheimer's GenomicsDB: A resource for exploring Alzheimer's disease genetic and genomic knowledge. Greenfest-Allen E, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 37881831
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  1. Sex-specific genetic architecture of late-life memory performance. Eissman JM, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 37984853
  2. Whole-Genome Sequencing Analysis Reveals New Susceptibility Loci and Structural Variants Associated with Progressive Supranuclear Palsy. Wang H, et al. medRxiv : the preprint server for health sciences. 2024. PMID: 38234807
  3. Admixture mapping identifies novel Alzheimer's disease risk regions in African Americans. Rajabli F, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 36539198
  4. Association of Common and Rare Variants with Alzheimer's Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer's Disease Sequencing Project. Lee WP, et al. medRxiv : the preprint server for health sciences. 2023. PMID: 37693521
  5. Associations of Sex, Race, and Apolipoprotein E Alleles With Multiple Domains of Cognition Among Older Adults. Walters S, et al. JAMA neurology. 2023. PMID: 37459083
  6. Identification of novel genes for age-at-onset of Alzheimer's disease by combining quantitative and survival trait analyses. Li YJ, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 36738287
  7. LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry. Katsumata Y, et al. Journal of neuropathology and experimental neurology. 2023. PMID: 37528055
  8. Neuropsychiatric features in a multi-ethnic population with Alzheimer disease and mild cognitive impairment. Celis K, et al. International journal of geriatric psychiatry. 2023. PMID: 37655494
  9. Structural Variation Detection and Association Analysis of Whole-Genome-Sequence Data from 16,905 Alzheimer's Diseases Sequencing Project Subjects. Wang H, et al. medRxiv : the preprint server for health sciences. 2023. PMID: 37745545
  10. The Early-Onset Alzheimer's Disease Whole-Genome Sequencing Project: Study design and methodology. Ray NR, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 37390458
  11. Alzheimer's Disease Variant Portal: A Catalog of Genetic Findings for Alzheimer's Disease. Kuksa PP, et al. Journal of Alzheimer's disease : JAD. 2022. PMID: 35068457
  12. An association test of the spatial distribution of rare missense variants within protein structures identifies Alzheimer's disease-related patterns. Jin B, et al. Genome research. 2022. PMID: 35210353
  13. Association of mitochondrial variants and haplogroups identified by whole exome sequencing with Alzheimer's disease. Zhang X, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 34152079
  14. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease. Holstege H, et al. Nature genetics. 2022. PMID: 36411364
  15. Mendelian randomization highlights causal association between genetically increased C-reactive protein levels and reduced Alzheimer's disease risk. Hu Y, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 35598332
  16. Multiple gene variants linked to Alzheimer's-type clinical dementia via GWAS are also associated with non-Alzheimer's neuropathologic entities. Katsumata Y, et al. Neurobiology of disease. 2022. PMID: 36191742
  17. Neuropathological lesions and their contribution to dementia and cognitive impairment in a heterogeneous clinical population. Godrich D, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 35142102
  18. Progranulin mutations in clinical and neuropathological Alzheimer's disease. Vardarajan BN, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 35258170
  19. Copy Number Variation Identification on 3,800 Alzheimer's Disease Whole Genome Sequencing Data from the Alzheimer's Disease Sequencing Project. Lee WP, et al. Frontiers in genetics. 2021. PMID: 34804120
  20. Large-scale sequencing studies expand the known genetic architecture of Alzheimer's disease. Xue D, et al. Alzheimer's & dementia (Amsterdam, Netherlands). 2021. PMID: 35005195
  21. Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus. Rajabli F, et al. Neurobiology of aging. 2021. PMID: 33902942
  22. Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics. Sariya S, et al. Annals of neurology. 2021. PMID: 34038570
  23. A rare missense variant of CASP7 is associated with familial late-onset Alzheimer's disease. Zhang X, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2019. PMID: 30503768
  24. Association of Rare Coding Mutations With Alzheimer Disease and Other Dementias Among Adults of European Ancestry. Patel D, et al. JAMA network open. 2019. PMID: 30924900
  25. Rare genetic variation implicated in non-Hispanic white families with Alzheimer disease. Beecham GW, et al. Neurology. Genetics. 2018. PMID: 30569016