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SCIENTIFIC LITERATURE · MED

Discovering genetic interactions bridging pathways in genome-wide association studies.

Nat Commun · 2019-09-19

DOI: 10.1038/s41467-019-12131-7PMID: 31537791

Open accessResearch Support, Non-U.S. Gov't; research-article; Journal Article; Research Support, N.I.H., ExtramuralOriginal source ↗

Research overview

The text below is the source article’s original abstract under a verified reuse license. cc by

Genetic interactions have been reported to underlie phenotypes in a variety of systems, but the extent to which they contribute to complex disease in humans remains unclear. In principle, genome-wide association studies (GWAS) provide a platform for detecting genetic interactions, but existing methods for identifying them from GWAS data tend to focus on testing individual locus pairs, which undermines statistical power. Importantly, a global genetic network mapped for a model eukaryotic organism revealed that genetic interactions often connect genes between compensatory functional modules in a highly coherent manner. Taking advantage of this expected structure, we developed a computational approach called BridGE that identifies pathways connected by genetic interactions from GWAS data. Applying BridGE broadly, we discover significant interactions in Parkinson's disease, schizophrenia, hypertension, prostate cancer, breast cancer, and type 2 diabetes. Our novel approach provides a general framework for mapping complex genetic networks underlying human disease from genome-wide genotype data.

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