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Functional disease architectures reveal unique biological role of transposable elements

Author

Listed:
  • Farhad Hormozdiari

    (Harvard T.H. Chan School of Public Health
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Bryce Geijn

    (Harvard T.H. Chan School of Public Health
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Joseph Nasser

    (Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Omer Weissbrod

    (Harvard T.H. Chan School of Public Health
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Steven Gazal

    (Harvard T.H. Chan School of Public Health
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Chelsea J. -T. Ju

    (University of California)

  • Luke O’ Connor

    (Harvard T.H. Chan School of Public Health
    Program in Bioinformatics and Integrative Genomics, Harvard Graduate School of Arts and Sciences)

  • Margaux L. A. Hujoel

    (Harvard T.H. Chan School of Public Health)

  • Jesse Engreitz

    (Program in Medical and Population Genetics, Broad Institute of MIT and Harvard)

  • Fereydoun Hormozdiari

    (University of California
    MIND Institute and UC-Davis Genome Center)

  • Alkes L. Price

    (Harvard T.H. Chan School of Public Health
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard
    Harvard T.H. Chan School of Public Health)

Abstract

Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as junk DNA, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases remains unknown. Here, we analyze data from 41 independent diseases and complex traits to draw three conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39 ± 2% of heritability), TE explain substantially more heritability than expected based on their depletion for known functional annotations. This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function. Third, Short Interspersed Nuclear Elements (SINE) are far more enriched for blood traits than for other traits. Our results can help elucidate the biological roles that TE play in the genetic architecture of diseases.

Suggested Citation

  • Farhad Hormozdiari & Bryce Geijn & Joseph Nasser & Omer Weissbrod & Steven Gazal & Chelsea J. -T. Ju & Luke O’ Connor & Margaux L. A. Hujoel & Jesse Engreitz & Fereydoun Hormozdiari & Alkes L. Price, 2019. "Functional disease architectures reveal unique biological role of transposable elements," Nature Communications, Nature, vol. 10(1), pages 1-8, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11957-5
    DOI: 10.1038/s41467-019-11957-5
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