Gene network analysis of small molecules with autoimmune disease associated genes predicts a novel strategy for drug efficacy

Autoimmun Rev. 2013 Feb;12(4):510-22. doi: 10.1016/j.autrev.2012.09.001. Epub 2012 Sep 18.

Abstract

Numerous genes/SNPs in autoimmune diseases (ADs) are identified through genome-wide association studies (GWAS) and likely to contribute in developing autoimmune phenotypes. Constructions of biologically meaningful pathways are necessary to determine how these genes interact with each other and with other small molecules to develop various complex AD phenotypes prior to beginning time-consuming rigorous experimentation. We have constructed biological pathways with genetically identified genes leading to shared AD phenotypes. Various environmental and endogenous factors interact with these AD associated genes suggesting their critical role in developing diseases and further association studies could be designed for assessing the role of these factors with risk allele in a specific gene. Additionally, existing drugs that have been used long before the identification of these genetically associated genes also interact with these newly associated genes. Thus advanced therapeutic strategies could be designed by grouping patients with risk allele(s) in particular genes that directly or closely interact with the specified drugs. This drug-susceptible gene network will not only increase our understanding about the additional molecular basis for effectiveness against these diseases but also indicate which drug could be more effective for those patients carrying risk allele(s) in that gene. Additionally, we have also identified several interlinking genes in the pathways that could be used for designing future association studies.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / genetics*
  • Autoimmunity / drug effects
  • Autoimmunity / genetics
  • Epistasis, Genetic
  • Gene Regulatory Networks*
  • Genome-Wide Association Study*
  • Humans
  • Pharmacogenetics
  • Phenotype