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Collaboration on Alzheimer Disease Research

PI
Pericak-Vance, Margaret
DAR ID
10014
Initial Approval Date
November 5, 2018
Current DAR Status
Expired
PI Institution
University of Miami
PI Institution Country
United States
PI Institution Type
Non-Profit

Requested Datasets (3)

NG00067Alzheimer's Disease Sequencing Project Umbrella StudyNG00106LASI-DAD Genotyping Chip Data (Illumina Infinium GSA-24 v2.0), Imputed Data (1000 Genomes Phase 3 v5 and TOPMed r2)NG00104Dataset from Clinical and Pathological Studies in the Oldest Old (90+ Study)

Research Use Statement
We plan to analyze GWAS, whole exome and whole genome sequence data generated from subjects with Alzheimer's disease (AD) and elderly normal controls. 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 versa. 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 (32)

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. No association of Alzheimer disease with the joint effect of HFE and TF in the mid-western Amish. Liu Y, et al. Journal of medical genetics. 2026. PMID: 41207713
  2. A multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations. Kurniansyah N, et al. medRxiv : the preprint server for health sciences. 2025. PMID: 41040715
  3. ABCA7 deletion lowers age at onset of Alzheimer's disease and interacts with APOE ε4 synergistically in African-ancestry populations. Akgun B, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. PMID: 40832784
  4. Alzheimer's disease multi-ancestry genome-wide interaction and stratified study with smoking. Dacey R, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. PMID: 41268768
  5. 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
  6. Domain mapping of disease mutations reveals pathogenic SORL1 variants in Alzheimer's disease. Andersen OM, et al. Molecular neurodegeneration. 2025. PMID: 41327266
  7. Examination of MGMT as a risk gene for dementia in the Amish. Main LR, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. PMID: 39711484
  8. Exploring potential mechanisms of an African protective locus for Alzheimer's disease in APOEε4 carriers. Bertholim-Nasciben L, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. PMID: 40704449
  9. Genome-wide association studies of Alzheimer's disease and related disorders stratified by sex, onset age, and Apolipoprotein E genotype reveal novel risk loci in African Americans. Sherva R, et al. Alzheimer's research & therapy. 2025. PMID: 40708016
  10. Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease. Rajabli F, et al. Genome biology. 2025. PMID: 40676597
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  1. Multi-omic derived cell-type specific Alzheimer disease polygenic risk scores. O'Neill N, et al. Neurobiology of aging. 2025. PMID: 40706314
  2. Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations. Nicolas A, et al. Nature genetics. 2025. PMID: 40533518
  3. X-chromosome-wide association study for Alzheimer's disease. Le Borgne J, et al. Molecular psychiatry. 2025. PMID: 39633006
  4. African origin haplotype protective for Alzheimer's disease in APOEε4 carriers: exploring potential mechanisms. Bertholim-Nasciben L, et al. bioRxiv : the preprint server for biology. 2024. PMID: 39484566
  5. Alzheimer's Disease Sequencing Project Release 4 Whole Genome Sequencing Dataset. Leung YY, et al. medRxiv : the preprint server for health sciences. 2024. PMID: 39677464
  6. 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
  7. Examining the Performance of Polygenic Risk Scores for Alzheimer Disease Within and Across Populations Using k-Fold Cross-Validation. Osterman MD, et al. Neurology. Genetics. 2024. PMID: 40881139
  8. Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry. Ray NR, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 38958117
  9. Generalizability of Tau and Amyloid Plasma Biomarkers in Alzheimer's Disease Cohorts of Diverse Genetic Ancestries. Griswold AJ, et al. medRxiv : the preprint server for health sciences. 2024. PMID: 38645114
  10. Genetic analyses in multiplex families confirms chromosome 5q35 as a risk locus for Alzheimer's Disease in individuals of African Ancestry. Nuytemans K, et al. Neurobiology of aging. 2024. PMID: 37952397
  11. Genome-wide association analysis and admixture mapping in a Puerto Rican cohort supports an Alzheimer disease risk locus on chromosome 12. Akgun B, et al. Frontiers in aging neuroscience. 2024. PMID: 39295643
  12. Human whole-exome genotype data for Alzheimer's disease. Leung YY, et al. Nature communications. 2024. PMID: 38263370
  13. Methylation Clocks Do Not Predict Age or Alzheimer's Disease Risk Across Genetically Admixed Individuals. Cruz-González S, et al. bioRxiv : the preprint server for biology. 2024. PMID: 39464059
  14. Missense and Loss of Function Variants at GWAS Loci in Familial Alzheimer's Disease. Gunasekaran TI, et al. medRxiv : the preprint server for health sciences. 2024. PMID: 38196599
  15. Missense and loss-of-function variants at GWAS loci in familial Alzheimer's disease. Gunasekaran TI, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 39233587
  16. MitoH3: Mitochondrial Haplogroup and Homoplasmic/Heteroplasmic Variant Calling Pipeline for Alzheimer's Disease Sequencing Project. Zhu C, et al. Journal of Alzheimer's disease reports. 2024. PMID: 38746629
  17. Novel early-onset Alzheimer-associated genes influence risk through dysregulation of glutamate, immune activation, and intracell signaling pathways. Cruchaga C, et al. Research square. 2024. PMID: 38883718
  18. Report of the APOE4 National Institute on Aging/Alzheimer Disease Sequencing Project Consortium Working Group: Reducing APOE4 in Carriers is a Therapeutic Goal for Alzheimer's Disease. Vance JM, et al. Annals of neurology. 2024. PMID: 38180638
  19. The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact. Kalaria R, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 38696263
  20. Genome-wide association and multi-omics studies identify MGMT as a novel risk gene for Alzheimer's disease among women. Chung J, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 35770850
  21. A locus at 19q13.31 significantly reduces the ApoE ε4 risk for Alzheimer's Disease in African Ancestry. Rajabli F, et al. PLoS genetics. 2022. PMID: 35788729
  22. 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