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

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
doi: https://doi.org/10.1101/251967
Phillip L De Jager
1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th street, New York, NY, USA.
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Yiyi Ma
1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th street, New York, NY, USA.
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Cristin McCabe
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Jishu Xu
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Badri N. Vardarajan
1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th street, New York, NY, USA.
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Daniel Felsky
1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th street, New York, NY, USA.
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Hans-Ulrich Klein
1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Medical Center, 630 West 168th street, New York, NY, USA.
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Charles C. White
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Mette A. Peters
3Sage Bionetworks, 1100 Fairview Avenue N. Seattle WA 98109, USA
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Ben Lodgson
3Sage Bionetworks, 1100 Fairview Avenue N. Seattle WA 98109, USA
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Parham Nejad
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Anna Tang
2Cell Circuits Program, Broad Institute, 415 Main street, Cambridge MA, USA
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Lara M. Mangravite
3Sage Bionetworks, 1100 Fairview Avenue N. Seattle WA 98109, USA
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Lei Yu
4Rush Alzehimer Disease Center, RUSH University, 600 South Paulina Street, Chicago IL 60612
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Chris Gaiteri
4Rush Alzehimer Disease Center, RUSH University, 600 South Paulina Street, Chicago IL 60612
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Sara Mostafavi
5Departments of Statistics and Medical Genetics and Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 West 28th Avenue, Vancouver, British Columbia, Canada
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Julie A. Schneider
4Rush Alzehimer Disease Center, RUSH University, 600 South Paulina Street, Chicago IL 60612
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David A. Bennett
4Rush Alzehimer Disease Center, RUSH University, 600 South Paulina Street, Chicago IL 60612
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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 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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Posted January 23, 2018.
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A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research
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
bioRxiv 251967; doi: https://doi.org/10.1101/251967
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A multi-omic atlas of the human frontal cortex for aging and Alzheimer's disease research
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
bioRxiv 251967; doi: https://doi.org/10.1101/251967

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