A network approach to exploring the functional basis of gene-gene epistatic interactions in disease susceptibility.
Bioinformatics
; 34(10): 1741-1749, 2018 05 15.
Article
in En
| MEDLINE
| ID: mdl-29329369
ABSTRACT
Motivation Individual genetic variants explain only a small fraction of heritability in some diseases. Some variants have weak marginal effects on disease risk, but their joint effects are significantly stronger when occurring together. Most studies on such epistatic interactions have focused on methods for identifying the interactions and interpreting individual cases, but few have explored their general functional basis. This was due to the lack of a comprehensive list of epistatic interactions and uncertainties in associating variants to genes. Results:
We conducted a large-scale survey of published research articles to compile the first comprehensive list of epistatic interactions in human diseases with detailed annotations. We used various methods to associate these variants to genes to ensure robustness. We found that these genes are significantly more connected in protein interaction networks, are more co-expressed and participate more often in the same pathways. We demonstrate using the list to discover novel disease pathways. Contact kevinyip@cse.cuhk.edu.hk. Supplementary information Supplementary data are available at Bioinformatics online.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proteins
/
Disease Susceptibility
/
Epistasis, Genetic
Limits:
Humans
Language:
En
Journal:
Bioinformatics
Journal subject:
INFORMATICA MEDICA
Year:
2018
Document type:
Article