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

用于衰老和阿尔茨海默病研究的人类额叶皮层多组学图谱

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作者:Philip 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

Abstract

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.

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