Functional disease architectures reveal unique biological role of transposable elements

Farhad Hormozdiari, Bryce van de 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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Article number4054
JournalNature communications
Issue number1
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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