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Long non-coding RNA gene regulation and trait associations across human tissues

O. M. de Goede, N. M. Ferraro, D. C. Nachun, A. S. Rao, F. Aguet, A. N. Barbeira, S. E. Castel, S. Kim-Hellmuth, Y. Park, A. J. Scott, B. J. Strober, GTEx Consortium, C. D. Brown, X. Wen, I. M. Hall, A. Battle, T. Lappalainen, H. K. Im, K. G. Ardlie, T. Quertermous, K. Kirkegaard, S. B. Montgomery
doi: https://doi.org/10.1101/793091
O. M. de Goede
1Department of Genetics, Stanford University, Stanford, CA, USA
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  • For correspondence: odegoede@stanford.edu smontgom@stanford.edu
N. M. Ferraro
2Biomedical Informatics Training Program, Stanford University, Stanford, CA, USA
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D. C. Nachun
3Department of Pathology, Stanford University, Stanford, CA, USA
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A. S. Rao
4Department of Bioengineering, Stanford University, Stanford, CA, USA
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F. Aguet
5The Broad Institute of MIT and Harvard, Cambridge, MA, USA
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A. N. Barbeira
6Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA
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S. E. Castel
7New York Genome Center, New York, NY, USA
8Department of Systems Biology, Columbia University, New York, NY, USA
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S. Kim-Hellmuth
7New York Genome Center, New York, NY, USA
8Department of Systems Biology, Columbia University, New York, NY, USA
9Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany
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Y. Park
10Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
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A. J. Scott
11McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
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B. J. Strober
12Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
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C. D. Brown
13Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
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X. Wen
14Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
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I. M. Hall
11McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA
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A. Battle
12Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA
15Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA
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T. Lappalainen
7New York Genome Center, New York, NY, USA
8Department of Systems Biology, Columbia University, New York, NY, USA
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H. K. Im
6Section of Genetic Medicine, Department of Medicine, The University of Chicago, Chicago, IL, USA
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K. G. Ardlie
5The Broad Institute of MIT and Harvard, Cambridge, MA, USA
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T. Quertermous
16Division of Cardiovascular Medicine and Cardiovascular Institute, Stanford University, Stanford, CA, USA
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K. Kirkegaard
1Department of Genetics, Stanford University, Stanford, CA, USA
17Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA
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S. B. Montgomery
1Department of Genetics, Stanford University, Stanford, CA, USA
3Department of Pathology, Stanford University, Stanford, CA, USA
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  • For correspondence: odegoede@stanford.edu smontgom@stanford.edu
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Abstract

Long non-coding RNA (lncRNA) genes are known to have diverse impacts on gene regulation. However, it is still a major challenge to distinguish functional lncRNAs from those that are byproducts of surrounding transcriptional activity. To systematically identify hallmarks of biological function, we used the GTEx v8 data to profile the expression, regulation, network relationships and trait associations of lncRNA genes across 49 tissues encompassing 87 distinct traits. In addition to revealing widespread differences in regulatory patterns between lncRNA and protein-coding genes, we identified novel disease-associated lncRNAs, such as C6orf3 for psoriasis and LINC01475/RP11-129J12.1 for ulcerative colitis. This work provides a comprehensive resource to interrogate lncRNA genes of interest and annotate cell type and human trait relevance.

One Sentence Summary lncRNA genes have distinctive regulatory patterns and unique trait associations compared to protein-coding genes.

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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 October 04, 2019.
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Long non-coding RNA gene regulation and trait associations across human tissues
O. M. de Goede, N. M. Ferraro, D. C. Nachun, A. S. Rao, F. Aguet, A. N. Barbeira, S. E. Castel, S. Kim-Hellmuth, Y. Park, A. J. Scott, B. J. Strober, GTEx Consortium, C. D. Brown, X. Wen, I. M. Hall, A. Battle, T. Lappalainen, H. K. Im, K. G. Ardlie, T. Quertermous, K. Kirkegaard, S. B. Montgomery
bioRxiv 793091; doi: https://doi.org/10.1101/793091
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Long non-coding RNA gene regulation and trait associations across human tissues
O. M. de Goede, N. M. Ferraro, D. C. Nachun, A. S. Rao, F. Aguet, A. N. Barbeira, S. E. Castel, S. Kim-Hellmuth, Y. Park, A. J. Scott, B. J. Strober, GTEx Consortium, C. D. Brown, X. Wen, I. M. Hall, A. Battle, T. Lappalainen, H. K. Im, K. G. Ardlie, T. Quertermous, K. Kirkegaard, S. B. Montgomery
bioRxiv 793091; doi: https://doi.org/10.1101/793091

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