Year: 2019
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1554504499, Statistical methods to localize disease heritability and identify biological mechanisms, Network-based prediction and validation of causal schizophrenia genes and variants, G5344811513, Harvard Training Program in Bioinformatics Applied to Diabetes, Obesity and Metabolism., Leveraging molecular QTL to understand the genetic architecture of disease, Functionally specialized components of disease heritability in ENCODE data, G9000286330, Training Grant in Quantitative Sciences for Cancer Research, Statistical methods to localize disease heritability and identify biological mechanisms, Functional and population genetic architectures of complex disease
OpenAlex ID: W2971473882