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A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research

By Phillip L. De Jager, Yiyi Ma, Cristin McCabe, Jishu Xu, Badri N. Vardarajan, Daniel Felsky, Hans-Ulrich Klein, Charles C White, Mette A. Peters, Ben Lodgson, Parham Nejad, Anna Tang, Lara M. Mangravite, Lei Yu, Chris Gaiteri, Sara Mostafavi, Julie A Schneider, David A. Bennett

Posted 23 Jan 2018
bioRxiv DOI: 10.1101/251967 (published DOI: 10.1038/sdata.2018.142)

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 and belong to a very few prospective studies of aging and dementia with detailed, longitudinal cognitive phenotyping during life and a quantitative, structured neuropathologic examination after death for >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.

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