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Description

The Colorado Adoption/Twin Study of Lifespan behavioral development & cognitive aging (CATSLife) aims are to: conduct a genetically sensitive study of individual differences in behavioral and cognitive change at the cusp of middle adulthood, in participants from the Colorado Adoption Project (CAP) and Longitudinal Twin Study (LTS) studied almost yearly from birth to early adulthood; map individual differences in growth and maintenance of cognitive abilities; evaluate and trace measured physical factors and health behaviors, biochemical markers and measured genetic pathways important to sustaining cognitive performance; and track measured environmental factors that might decrease, sustain or boost cognitive performance. (R01 AG046938 co-PI’s: Reynolds (contact), Wadsworth)

This data release includes data from 1,245 respondents who provided consent to share data and were included in a study of APOE isoforms and IQ data with up to three assessments across childhood and adolescence. [PMCID: PMC6800620]

Sample Summary per Data Type

Sample SetAccessionData TypeNumber of Samples
CATSLife APOEsnd10078Targeted genotyping1,245

Available Filesets

NameAccessionLatest ReleaseDescription
CATSLife: APOE isoforms, IQ datafsa000097NG00145.v1APOE isforms, IQ data

View the File Manifest for a full list of files released in this dataset.

This data release includes data from 1,245 respondents who provided consent to share data and were included in a study of APOE isoforms and IQ data with up to three assessments across childhood and adolescence [PMCID: PMC6800620].

Sample SetAccession NumberNumber of SubjectsNumber of Samples
CATSLife APOEsnd100781,2451,245
Consent LevelNumber of Subjects
HMB-IRB-PUB-NPU-MDS1,245

Visit the Data Use Limitations page for definitions of the consent levels above.

Total number of approved DARs: 1
  • Investigator:
    Cruchaga, Carlos
    Institution:
    Washington University School of Medicine
    Project Title:
    The Familial Alzheimer Sequencing (FASe) Project
    Date of Approval:
    May 9, 2024
    Request status:
    Approved
    Research use statements:
    Show statements
    Technical Research Use Statement:
    The goal of this study is to identify new genes and mutations that cause or increase risk for Alzheimer disease (AD), as well as protective factors. Individuals and families were selected from the Knight-ADRC (Washington University) and the NIA-LOAD study. Only families with at least three first-degree affected individuals were included. Families with pathogenic variants in the known AD or FTD genes, or in which APOE4 segregated with disease were excluded. At least two cases and one control were selected per family. Cases had an age at onset (AAO) after 65 yo and controls had a larger age at last assessment than the latest AAO within the family. Whole exome (WES) and whole genome sequencing (WGS) was generated for 1,235 individuals (285 families) that together with data from our collaborators and the ADSP family-based cohort (3,449 individuals and 757 families) will provide enough statistical power to identify new genes for AD. Dr. Tanzi (Harvard Medical School) will provide WGS from 400 families from the NIMH Alzheimer disease genetics initiative study. We will perform single variant and gene-based analyses to identify genes and variants that increase risk for disease in AD families. Single variant analysis will consist of a combination of association and segregation analyses. We will run family-based gene-based methods to identify genes that show and overall enrichment of variants in AD cases. We will also look for protective and modifier variants. To do this we will identify families loaded with AD cases, that also include individuals with a high burden of known risk variants but that do not develop the disease (escapees). We will use the sequence data and the family structure to identify variants that segregate with the escapee phenotype. The most promising variants and genes will be replicated in independent datasets (ADSP case-control, ADNI, Knight-ADRC, NIA-LOAD ). We will perform single variant and gene-based analyses to replicate the initial findings, and survival analysis to replicate the protective variants. We will select the most promising variants/genes for functional studies
    Non-Technical Research Use Statement:
    Family-based approaches led to the identification of disease-causing Alzheimer’s Disease (AD) variants in the genes encoding APP, PSEN1 and PSEN2. The identification of these genes led to the A?-cascade hypothesis and to the development of drugs that target this pathway. Recently, we have identified rare coding variants in TREM2, ABCA7, PLD3 and SORL1 with large effect sizes for risk for AD, confirming that rare coding variants play a role in the etiology of AD. In this proposal, we will identify rare risk and protective alleles using sequence data from families densely affected by AD. We hypothesize that these families are enriched for genetic risk factors. We already have sequence data from 695 families (2,462 individuals), that combined with the ADSP and the NIMH dataset will lead to a dataset of more than 1,042 families (4,684 individuals). Our preliminary results support the flexibility of this approach and strongly suggest that protective and risk variants with large effect size will be found, which will lead to a better understanding of the biology of the disease.

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

Use the study-specific acknowledgement statements below (as applicable):

For investigators using any data from this dataset:

Please cite/reference the use of NIAGADS data by including the accession NG00145.

For investigators using The Colorado Adoption/Twin Study of Lifespan behavioral development & cognitive aging (CATSLife) (sa000046) data:

The Colorado Adoption/Twin Study of Lifespan behavioral development & cognitive aging (CATSLife) project is supported by the National Institute on Aging (grant number NIA R01AG046938) and conducted at the University of Colorado Boulder.

  • Reynolds, C. A., Smolen, A., Corley, R. P., Munoz, E., Friedman, N. P., Rhee, S. H., Stallings, M. C., DeFries, J. C., & Wadsworth, S. J. (2019, Dec). APOE effects on cognition from childhood to adolescence. Neurobiol Aging, 84, 239.e231-239.e238. https://doi.org/10.1016/j.neurobiolaging.2019.04.011 PubMed link
  • Wadsworth, S. J., Corley, R. P., Munoz, E., Trubenstein, B. P., Knaap, E., DeFries, J. C., Plomin, R., & Reynolds, C. A. (2019, Dec). CATSLife: A Study of Lifespan Behavioral Development and Cognitive Functioning. Twin Res Hum Genet, 22(6), 695-706. https://doi.org/10.1017/thg.2019.49 PubMed link