Nearly all common complex diseases are heritable: we are not all equally susceptible to the environmental and behavioural risk factors that trigger them, and these inter-individual differences are in part genetic. GWAS conducted in the last decade show that this heritability is driven by hundreds to thousands of genetic variants scattered across the genome. A minority of those are coding variants that act by changing the amino-acid sequence of the encoded protein. The majority are regulatory variants, which act by perturbing gene switches thereby altering the expression profile of one or more target genes. Such variant-dependent perturbations of gene expression are also known as expression Quantitative Trait Loci (eQTL).
To aid in the identification of the causative genes that are perturbed by disease-causing regulatory variants, we have generated a transcriptome data set of nine disease relevant cell types (CD4, CD8, CVD19, CD14, CD15, platelets, ileonic, colonic and rectal biopsies) in 300 healthy European individuals. Using this data, we have identified 24,000 cis-eQTL reflecting the effects of 9,700 distinct regulatory modules (constellations of regulatory variants). We have developed a metric, ϑ, to identify cis-eQTL that match disease association patterns (DAP) and could therefore drive the disease. The CEDAR website provides a genome-wide overview of the corresponding results for important common complex diseases.
, Ilya Altukhov2
, Dimitry Alexeev2,3
, Yuri Aulchenko3,4
, Michel Georges1
Unit of Animal Genomics, WELBIO, GIGA & Faculty of Veterinary Medicine, University of Liege, Belgium; 2
Moscow Institute of Physics and Technology, Russia; 3
Institute of Cytology and Genetics, Novosibirsk State University, Russia. 4
PolyOmica, 's-Hertogenbosch, The Netherlands.
CEDAR was funded by grants to Michel Georges from WELBIO (CAUSIBD), BELSPO (BeMGI), and Horizon 2020 (SYSCID).
Momozawa et al. Risk loci for inflammatory bowel disease are enriched in multigenic regulatory modules that act across cell types and encompass causative genes. (2018) Nat Communication, in press.
Using CEDAR: link to user guide
Downloading CEDAR data:
Array Express E-MTAB-6666 and E-MTAB-6667 or link to data