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Alzheimer Disease Sequence Analysis Collaborative (a.k.a. Collaborative Alzheimer Disease REsearch; CADRE)

PI
Haines, Jonathan
DAR ID
10011
Initial Approval Date
October 22, 2018
Current DAR Status
Active
PI Institution
Case Western Reserve University
PI Institution Country
United States
PI Institution Type
Non-Profit

Requested Datasets (1)

NG00067Alzheimer's Disease Sequencing Project Umbrella Study

Research Use Statement

We plan to analyze whole exome and whole genome sequence data generated from subjects with Alzheimer disease (AD) and elderly normal controls. The goal of the planned analyses is to identify genes and other functional elements that have variations 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 data. We will also evaluate similar sequence data from multiplex AD families to identify variants associated with AD risk and protection, and evaluate variant co-segregation with AD. We also will focus on structural variants (insertion-deletions, copy number variants, and chromosomal rearrangements) detected using both whole genome and whole exome data. All data will be analyzed separately and in an integrated fashion and will incorporate additional genetic and functional 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 two 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 (74)

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. African Ancestry Individuals with Higher Educational Attainment Are Resilient to Alzheimer's Disease Measured by pTau181. Rajabli F, et al. Journal of Alzheimer's disease : JAD. 2024. PMID: 38393909
  2. 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
  3. Genome-wide association studies identify novel loci in rapidly progressive Alzheimer's disease. Wang P, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024. PMID: 38184787
  4. 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
  5. Genetic variants in the SHISA6 gene are associated with delayed cognitive impairment in two family datasets. Ramos J, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 35490390
  6. Midlife lipid and glucose levels are associated with Alzheimer's disease. Zhang X, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2023. PMID: 35319157
  7. Admixture Mapping of Alzheimer's disease in Caribbean Hispanics identifies a new locus on 22q13.1. Kizil C, et al. Molecular psychiatry. 2022. PMID: 35365809
  8. Alzheimer's disease associated AKAP9 I2558M mutation alters posttranslational modification and interactome of tau and cellular functions in CRISPR-edited human neuronal cells. You Y, et al. Aging cell. 2022. PMID: 35567427
  9. 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
  10. Blood and brain transcriptome analysis reveals APOE genotype-mediated and immune-related pathways involved in Alzheimer disease. Panitch R, et al. Alzheimer's research & therapy. 2022. PMID: 35139885
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  1. Correlation of plasma and neuroimaging biomarkers in Alzheimer's disease. Brickman AM, et al. Annals of clinical and translational neurology. 2022. PMID: 35306760
  2. Dementia in Africa: Current evidence, knowledge gaps, and future directions. Akinyemi RO, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 34569714
  3. FMNL2 regulates gliovascular interactions and is associated with vascular risk factors and cerebrovascular pathology in Alzheimer's disease. Lee AJ, et al. Acta neuropathologica. 2022. PMID: 35608697
  4. Identifying differential regulatory control of APOE ɛ4 on African versus European haplotypes as potential therapeutic targets. Nuytemans K, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 34978147
  5. Manifestations of Alzheimer's disease genetic risk in the blood are evident in a multiomic analysis in healthy adults aged 18 to 90. Heath L, et al. Scientific reports. 2022. PMID: 35413975
  6. Midlife Vascular Factors and Prevalence of Mild Cognitive Impairment in Late-Life in Mexico. Arce Rentería M, et al. Journal of the International Neuropsychological Society : JINS. 2022. PMID: 34376262
  7. 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
  8. New insights into the genetic etiology of Alzheimer's disease and related dementias. Bellenguez C, et al. Nature genetics. 2022. PMID: 35379992
  9. 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
  10. Protein phosphatase 2A and complement component 4 are linked to the protective effect of APOE ɛ2 for Alzheimer's disease. Jun GR, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 35142023
  11. Social network characteristics moderate associations between cortical thickness and cognitive functioning in older adults. Sharifian N, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 34002926
  12. The National Institute on Aging Late-Onset Alzheimer's Disease Family Based Study: A resource for genetic discovery. Reyes-Dumeyer D, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2022. PMID: 34978149
  13. A missense variant in SHARPIN mediates Alzheimer's disease-specific brain damages. Park JY, et al. Translational psychiatry. 2021. PMID: 34785643
  14. Association of Dietary Prebiotic Consumption with Reduced Risk of Alzheimer's Disease in a Multiethnic Population. Nishikawa M, et al. Current Alzheimer research. 2021. PMID: 34951365
  15. Association of Life's Simple 7 with incident dementia and its modification by the apolipoprotein E genotype. Guo J, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021. PMID: 33938146
  16. Association of Regional White Matter Hyperintensities With Longitudinal Alzheimer-Like Pattern of Neurodegeneration in Older Adults. Rizvi B, et al. JAMA network open. 2021. PMID: 34609497
  17. Common variants in Alzheimer's disease and risk stratification by polygenic risk scores. de Rojas I, et al. Nature communications. 2021. PMID: 34099642
  18. 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
  19. Genetically regulated expression in late-onset Alzheimer's disease implicates risk genes within known and novel loci. Chen HH, et al. Translational psychiatry. 2021. PMID: 34873149
  20. Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. DeMichele-Sweet MAA, et al. Molecular psychiatry. 2021. PMID: 34112972
  21. Increased APOE ε4 expression is associated with the difference in Alzheimer's disease risk from diverse ancestral backgrounds. Griswold AJ, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021. PMID: 33522086
  22. Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease. Panitch R, et al. Molecular psychiatry. 2021. PMID: 34480088
  23. KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer's Disease. Siddiqui T, et al. Cells. 2021. PMID: 34685728
  24. 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
  25. Linkage of Alzheimer disease families with Puerto Rican ancestry identifies a chromosome 9 locus. Rajabli F, et al. Neurobiology of aging. 2021. PMID: 33902942
  26. Novel Alzheimer Disease Risk Loci and Pathways in African American Individuals Using the African Genome Resources Panel: A Meta-analysis. Kunkle BW, et al. JAMA neurology. 2021. PMID: 33074286
  27. Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants. Damotte V, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2021. PMID: 34002480
  28. Polygenic Risk Score for Alzheimer's Disease in Caribbean Hispanics. Sariya S, et al. Annals of neurology. 2021. PMID: 34038570
  29. Analysis of brain region-specific co-expression networks reveals clustering of established and novel genes associated with Alzheimer disease. Lancour D, et al. Alzheimer's research & therapy. 2020. PMID: 32878640
  30. Association between alcohol consumption and Alzheimer's disease: A Mendelian randomization study. Andrews SJ, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2020. PMID: 31786126
  31. Association Between Common Variants in RBFOX1, an RNA-Binding Protein, and Brain Amyloidosis in Early and Preclinical Alzheimer Disease. Raghavan NS, et al. JAMA neurology. 2020. PMID: 32568366
  32. Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition. Writing Committee for the ENIGMA-CNV Working Group, et al. JAMA psychiatry. 2020. PMID: 31665216
  33. Circulating Vitamin D Levels and Alzheimer's Disease: A Mendelian Randomization Study in the IGAP and UK Biobank. Wang L, et al. Journal of Alzheimer's disease : JAD. 2020. PMID: 31815694
  34. Differences in plasma metabolites related to Alzheimer's disease, APOE ε4 status, and ethnicity. Vardarajan B, et al. Alzheimer's & dementia (New York, N. Y.). 2020. PMID: 32377558
  35. Exceptionally low likelihood of Alzheimer's dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Reiman EM, et al. Nature communications. 2020. PMID: 32015339
  36. Failure to detect synergy between variants in transferrin and hemochromatosis and Alzheimer's disease in large cohort. Vance E, et al. Neurobiology of aging. 2020. PMID: 32143980
  37. Hadoop and PySpark for reproducibility and scalability of genomic sequencing studies. Wheeler NR, et al. Pacific Symposium on Biocomputing. Pacific Symposium on Biocomputing. 2020. PMID: 31797624
  38. Insoluble Tau From Human FTDP-17 Cases Exhibit Unique Transmission Properties In Vivo. Weitzman SA, et al. Journal of neuropathology and experimental neurology. 2020. PMID: 32838419
  39. Interplay between Socioeconomic Markers and Polygenic Predisposition on Timing of Dementia Diagnosis. Ajnakina O, et al. Journal of the American Geriatrics Society. 2020. PMID: 32187654
  40. LRP10 variants in progressive supranuclear palsy. Vergouw LJM, et al. Neurobiology of aging. 2020. PMID: 32527607
  41. MAPT haplotype-stratified GWAS reveals differential association for AD risk variants. Strickland SL, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2020. PMID: 32400971
  42. Sex-dependent autosomal effects on clinical progression of Alzheimer's disease. Fan CC, et al. Brain : a journal of neurology. 2020. PMID: 32591829
  43. Transmission of tauopathy strains is independent of their isoform composition. He Z, et al. Nature communications. 2020. PMID: 31911587
  44. Two-stage Bayesian GWAS of 9576 individuals identifies SNP regions that are targeted by miRNAs inversely expressed in Alzheimer's and cancer. Pathak GA, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2020. PMID: 31914222
  45. Use of local genetic ancestry to assess TOMM40-523' and risk for Alzheimer disease. Bussies PL, et al. Neurology. Genetics. 2020. PMID: 32337333
  46. 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
  47. 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
  48. Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype. Ma Y, et al. JAMA neurology. 2019. PMID: 31180460
  49. APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer's Disease Risk in a Multiracial Sample. Choi KY, et al. Journal of clinical medicine. 2019. PMID: 31426376
  50. 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
  51. Association of Variants in PINX1 and TREM2 With Late-Onset Alzheimer Disease. Tosto G, et al. JAMA neurology. 2019. PMID: 31058951
  52. CpG-related SNPs in the MS4A region have a dose-dependent effect on risk of late-onset Alzheimer disease. Ma Y, et al. Aging cell. 2019. PMID: 31144443
  53. Current and past leisure time physical activity in relation to risk of Alzheimer's disease in older adults. Ogino E, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2019. PMID: 31587996
  54. Gene-based analysis in HRC imputed genome wide association data identifies three novel genes for Alzheimer's disease. Baker E, et al. PloS one. 2019. PMID: 31283791
  55. Genetic and epigenetic study of an Alzheimer's disease family with monozygotic triplets. Zhang M, et al. Brain : a journal of neurology. 2019. PMID: 31580390
  56. Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Kunkle BW, et al. Nature genetics. 2019. PMID: 30820047
  57. Inferring the Molecular Mechanisms of Noncoding Alzheimer's Disease-Associated Genetic Variants. Amlie-Wolf A, et al. Journal of Alzheimer's disease : JAD. 2019. PMID: 31561366
  58. Quality control and integration of genotypes from two calling pipelines for whole genome sequence data in the Alzheimer's disease sequencing project. Naj AC, et al. Genomics. 2019. PMID: 29857119
  59. RNA editing alterations in a multi-ethnic Alzheimer disease cohort converge on immune and endocytic molecular pathways. Gardner OK, et al. Human molecular genetics. 2019. PMID: 31162550
  60. Secular trends in cognitive trajectories of diverse older adults. Vonk JMJ, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2019. PMID: 31672483
  61. Sex differences in the genetic predictors of Alzheimer's pathology. Dumitrescu L, et al. Brain : a journal of neurology. 2019. PMID: 31497858
  62. Sex/gender differences in cognitive trajectories vary as a function of race/ethnicity. Avila JF, et al. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2019. PMID: 31606366
  63. The Puerto Rico Alzheimer Disease Initiative (PRADI): A Multisource Ascertainment Approach. Feliciano-Astacio BE, et al. Frontiers in genetics. 2019. PMID: 31275353
  64. Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. Rajabli F, et al. PLoS genetics. 2018. PMID: 30517106