DIDA: the first digenic disease database

Although there exist many human disease-related genetic variant databases (e.g. HGMD, SwissVar), no public effort has been made to organize these data so that one can investigate the oligo- and polygenic nature of their disease-of-interest. However, it has been shown that many disorders, classically considered as monogenic, may be better explained by more complex inheritance mechanisms. One example can be found in those diseases with imperfect genotype-phenotype correlations, which might, in a monogenic context, be considered as showing reduced penetrance, but could in fact also be explained by a digenic inheritance model. This example pinpoints the need to develop new databases and services focused on complex inheritance models.
Here we present DIDA (DIgenic DAtabase): a manually curated database collecting human digenic disease instances. DIDA was created by collecting all digenic disease data published in scientific literature until December 2014. We manually screened the literature to ensure the high quality of this ex novo digenic database. For every publication describing patients with a disease explained by a digenic inheritance model, we annotated causative variant-pairs and enriched every instance with different features. These features include variant- and gene information with genomic-, cDNA- and protein coordinates, information regarding the functional effects of the va- riants, disease name and OMIM-id, clinical symptoms with HPO-terms and a digenic effect category (influence on the presence, severity, age-of-onset or symptoms of the disease). As such, this database forms a basis for understanding how the interplay and weight of variants leads to disease, which in turn may provide novel insights into diseases classically considered as monogenic.