SNP by SNP by environment interaction network of alcoholism

BMC Syst Biol. 2017 Mar 14;11(Suppl 3):19. doi: 10.1186/s12918-017-0403-7.


Background: Alcoholism has a strong genetic component. Twin studies have demonstrated the heritability of a large proportion of phenotypic variance of alcoholism ranging from 50-80%. The search for genetic variants associated with this complex behavior has epitomized sequence-based studies for nearly a decade. The limited success of genome-wide association studies (GWAS), possibly precipitated by the polygenic nature of complex traits and behaviors, however, has demonstrated the need for novel, multivariate models capable of quantitatively capturing interactions between a host of genetic variants and their association with non-genetic factors. In this regard, capturing the network of SNP by SNP or SNP by environment interactions has recently gained much interest.

Results: Here, we assessed 3,776 individuals to construct a network capable of detecting and quantifying the interactions within and between plausible genetic and environmental factors of alcoholism. In this regard, we propose the use of first-order dependence tree of maximum weight as a potential statistical learning technique to delineate the pattern of dependencies underpinning such a complex trait. Using a predictive based analysis, we further rank the genes, demographic factors, biological pathways, and the interactions represented by our SNP [Formula: see text]SNP[Formula: see text]E network. The proposed framework is quite general and can be potentially applied to the study of other complex traits.

Keywords: Alcoholism; Environment; GWAS; Interaction; Network; SNP.

MeSH terms

  • Alcoholism / genetics*
  • Gene-Environment Interaction*
  • Genome-Wide Association Study
  • Humans
  • Polymorphism, Single Nucleotide*
  • Racial Groups / genetics
  • Systems Biology*