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ADSP Data Analysis

PI
Farrer, Lindsay
DAR ID
10013
Initial Approval Date
October 29, 2018
Current DAR Status
Active
PI Institution
Boston University School of Medicine
PI Institution Country
United States
PI Institution Type
Non-Profit

Requested Datasets (12)

NG00067Alzheimer's Disease Sequencing Project Umbrella StudyNG00108Profiling microglia expression profiles in AD using single-nuclei RNA-seqNG00106LASI-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)NG00119Health and Retirement Study Genotype Data 2006-2012NG00121Alzheimer’s disease single-neuron whole-genome sequencing - Miller 2022NG00149ADC13 - Alzheimer's Disease Center Dataset 13NG00150ADC14 - Alzheimer's Disease Center Dataset 14NG00151ADC15 - Alzheimer's Disease Center Dataset 15NG00175Genome-wide association study of neuropathology endophenotypesNG00167Brain Small RNA Transcriptomics for AD and Related DementiasNG00176CNVs from ADSP WES data using CANOES software

Research Use Statement
As part of the Consortium for Alzheimers Sequence Analysis (CASA: NIA grant UF1-AG047133), 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 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 (25)

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. Multi-ancestry exome-wide study identifies variants associated with Alzheimer's disease protection. Khurshid Z, et al. Journal of Alzheimer's disease : JAD. 2026. PMID: 41428483
  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. 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
  4. 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
  5. A comparative study of structural variant calling in WGS from Alzheimer's disease families. Malamon JS, et al. Life science alliance. 2024. PMID: 38418088
  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. Blood-derived mitochondrial DNA copy number is associated with Alzheimer disease, Alzheimer-related biomarkers and serum metabolites. Tong T, et al. Alzheimer's research & therapy. 2024. PMID: 39444005
  8. DNA from multiple viral species is associated with Alzheimer's disease risk. Tejeda M, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 37578203
  9. Human whole-exome genotype data for Alzheimer's disease. Leung YY, et al. Nature communications. 2024. PMID: 38263370
  10. 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
Show more
  1. Whole-genome sequencing study in Koreans identifies novel loci for Alzheimer's disease. Kang M, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 39428694
  2. A haptoglobin (HP) structural variant alters the effect of APOE alleles on Alzheimer's disease. Bai H, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 37051669
  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. APOE Genotype and Alzheimer Disease Risk Across Age, Sex, and Population Ancestry. Belloy ME, et al. JAMA neurology. 2023. PMID: 37930705
  5. Association of African Ancestry-Specific APOE Missense Variant R145C With Risk of Alzheimer Disease. Le Guen Y, et al. JAMA. 2023. PMID: 36809323
  6. Novel loci for Alzheimer's disease identified by a genome-wide association study in Ashkenazi Jews. Li D, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 37260021
  7. 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
  8. 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
  9. 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
  10. 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
  11. Set-Based Rare Variant Expression Quantitative Trait Loci in Blood and Brain from Alzheimer Disease Study Participants. Patel D, et al. Genes. 2021. PMID: 33804025
  12. Whole exome sequencing study identifies novel rare and common Alzheimer's-Associated variants involved in immune response and transcriptional regulation. Bis JC, et al. Molecular psychiatry. 2020. PMID: 30108311
  13. 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
  14. Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype. Ma Y, et al. JAMA neurology. 2019. PMID: 31180460
  15. 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