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.
| Original language | English (US) |
|---|---|
| Article number | 4054 |
| Journal | Nature communications |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2019 |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
Functional disease architectures reveal unique biological role of transposable elements. / Hormozdiari, Farhad; van de Geijn, Bryce; Nasser, Joseph; Weissbrod, Omer; Gazal, Steven; Ju, Chelsea J.T.; Connor, Luke O.; Hujoel, Margaux L.A.; Engreitz, Jesse; Hormozdiari, Fereydoun; Price, Alkes L.
In: Nature communications, Vol. 10, No. 1, 4054, 01.12.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Functional disease architectures reveal unique biological role of transposable elements
AU - Hormozdiari, Farhad
AU - van de Geijn, Bryce
AU - Nasser, Joseph
AU - Weissbrod, Omer
AU - Gazal, Steven
AU - Ju, Chelsea J.T.
AU - Connor, Luke O.
AU - Hujoel, Margaux L.A.
AU - Engreitz, Jesse
AU - Hormozdiari, Fereydoun
AU - Price, Alkes L.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-019-11957-5
DO - 10.1038/s41467-019-11957-5
M3 - Article
C2 - 31492842
AN - SCOPUS:85071896849
VL - 10
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4054
ER -