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Brain xQTL map: Integrating the genetic architecture of the human brain transcriptome and epigenome

B Ng, CC White, H Klein, SK Sieberts, C McCabe, E Patrick, J Xu, L Yu, C Gaiteri, DA Bennett, S Mostafavi, De Jager PL
doi: https://doi.org/10.1101/142927
B Ng
1Department of Statistics and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
2Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.
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CC White
3Broad Institute, Cambridge, Massachusetts, USA.
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H Klein
3Broad Institute, Cambridge, Massachusetts, USA.
4Center for Translational & Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
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SK Sieberts
5Sage Bionetworks, Seattle, Washington, USA.
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C McCabe
3Broad Institute, Cambridge, Massachusetts, USA.
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E Patrick
3Broad Institute, Cambridge, Massachusetts, USA.
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J Xu
3Broad Institute, Cambridge, Massachusetts, USA.
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L Yu
6Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
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C Gaiteri
6Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
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DA Bennett
6Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
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S Mostafavi
1Department of Statistics and Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
2Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada.
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  • For correspondence: pdejager@rics.bwh.harvard.edu saram@stat.ubc.ca
De Jager PL
3Broad Institute, Cambridge, Massachusetts, USA.
4Center for Translational & Systems Neuroimmunology, Department of Neurology, Columbia University Medical Center, New York, New York, USA.
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  • For correspondence: pdejager@rics.bwh.harvard.edu saram@stat.ubc.ca
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Abstract

We perform quantitative trait locus (xQTL) analyses on a multi-omic dataset, comprising RNA sequence, DNA methylation, and histone acetylation ChIP sequence data from the dorsolateral prefrontal cortex of 411 older adult individuals. We identify SNPs that are significantly associated with gene expression, DNA methylation, and histone modification levels. Many SNPs influence more than one type of molecular feature, and epigenetic features are shown to mediate eQTLs in a number of (9%) such loci. We illustrate the utility of our new resource, xQTL Serve, in prioritizing the cell type most affected by an xQTL and in enhancing genome wide association studies (GWAS) as we report 18 additional CNS disease susceptibility loci after re-analyzing published studies.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted July 07, 2017.
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Brain xQTL map: Integrating the genetic architecture of the human brain transcriptome and epigenome
B Ng, CC White, H Klein, SK Sieberts, C McCabe, E Patrick, J Xu, L Yu, C Gaiteri, DA Bennett, S Mostafavi, De Jager PL
bioRxiv 142927; doi: https://doi.org/10.1101/142927
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Brain xQTL map: Integrating the genetic architecture of the human brain transcriptome and epigenome
B Ng, CC White, H Klein, SK Sieberts, C McCabe, E Patrick, J Xu, L Yu, C Gaiteri, DA Bennett, S Mostafavi, De Jager PL
bioRxiv 142927; doi: https://doi.org/10.1101/142927

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