A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research.
paper
Cited
Public
- Authors
- De Jager, Philip L; Ma, Yiyi; McCabe, Cristin; Xu, Jishu; Vardarajan, Badri N; Felsky, Daniel; Klein, Hans-Ulrich; White, Charles C; Peters, Mette A; Lodgson, Ben; Nejad, Parham; Tang, Anna; Mangravite, Lara M; Yu, Lei; Gaiteri, Chris; Mostafavi, Sara; Schneider, Julie A; Bennett, David A
- Year
- 2018
- Journal
- Scientific data
- PMID
- 30084846
- DOI
- 10.1038/sdata.2018.142
- PMCID
- PMC6080491
We initiated the systematic profiling of the dorsolateral prefrontal cortex obtained from a subset of autopsied individuals enrolled in the Religious Orders Study (ROS) or the Rush Memory and Aging Project (MAP), which are jointly designed prospective studies of aging and dementia with detailed, longitudinal cognitive phenotyping during life and a quantitative, structured neuropathologic examination after death. They include over 3,322 subjects. Here, we outline the first generation of data including genome-wide genotypes (n=2,090), whole genome sequencing (n=1,179), DNA methylation (n=740), chromatin immunoprecipitation with sequencing using an anti-Histone 3 Lysine 9 acetylation (H3K9Ac) antibody (n=712), RNA sequencing (n=638), and miRNA profile (n=702). Generation of other omic data including ATACseq, proteomic and metabolomics profiles is ongoing. Thanks to its prospective design and recruitment of older, non-demented individuals, these data can be repurposed to investigate a large number of syndromic and quantitative neuroscience phenotypes. The many subjects that are cognitively non-impaired at death also offer insights into the biology of the human brain in older non-impaired individuals.
Overlap of the different layers of βomicβ data.The venn diagram illustrates the extent to which the different layers of overlap in the ROS and MAP subjects that have been processed to date. 458 subjects have all layers of data described in this report.
Overlaps between pathologic and clinical diagnosis of Alzheimerβs dementia in ROSMAP.We illustrate the distribution of clinical diagnoses found in the ROSMAP subjects that meet a pathologic diagnosis of AD and in those that do not. We used the NIA-REAGAN guidelines for a pathologic diagnosis of AD, and all subjects were diagnosed as either having AD (AD_REGAN=1) or not (AD_RAEGAN=0). The clinical diagnosis of Alzheimerβs dementia was performed based on a review of all available clinical data by neurologists with expertise in dementia. Participants not fulfilling diagnostic criteria for AD dementia were classified as having mild cognitive impairment, being cognitively non-impaired, and having another form of dementia.
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