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Complex disease

Piecing together the puzzle of coronary artery disease

Nature Reviews Genetics volume 15, pages 572–573 (2014)Cite this article

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Mäkinen et al. determined CAD-associated SNPs from 16 independent GWASs and linked them with their empirically defined target genes using data from expression quantitative trait locus (eQTL) studies of CAD-related cell types and tissues. The resultant expression SNPs (eSNPs) were grouped into 'supersets' of functionally related genes on the basis of both known biological pathways and transcriptome-based co-regulated genes.

The researchers then used Bayesian network models (that is, graphical models that encode probabilistic relationships among variables of interest) to construct tissue-specific gene–gene interaction networks, which enabled them to identify the key driver genes at the centre of the supersets of CAD-associated genes. Among these genes, glyoxalase I (GLO1) and peptidylprolyl isomerase 1 (PPIL1), which are linked to antigen-processing genes in networks, were found to significantly affect expression levels of CAD-related genes in subsequent knockdown experiments using small interfering RNAs (siRNAs).

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References

  1. Mäkinen, V.-P. et al. Integrative genomics reveals novel molecular pathways and gene networks for coronary artery disease. PLoS Genet. 10, e1004502 (2014)

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  1. Esther Lau
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Lau, E. Piecing together the puzzle of coronary artery disease. Nat Rev Genet 15, 572–573 (2014). https://doi.org/10.1038/nrg3799

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