A method to associate all possible combinations of genetic and environmental factors using GxE landscape plot.
Genome-wide association studies (GWAS) and linkage analysis has identified many single nucleotide polymorphisms (SNPs) related to disease. There are many unknown SNPs whose minor allele frequencies (MAFs) as low as 0.005 having intermediate effects with odds ratio between 1.5~3.0. Low frequency variants having intermediate effects on disease pathogenesis are believed to have complex interactions with environmental factors called gene-environment interactions (GxE). Hence, we describe a model using 3D Manhattan plot called GxE landscape plot to visualize the association of p-values for gene-environment interactions (GxE). We used the Gene-Environment iNteraction Simulator 2 (GENS2) program to simulate interactions between two genetic loci and one environmental factor in this exercise. The dataset used for training contains disease status, gender, 20 environmental exposures and 100 genotypes for 170 subjects, and p-values were calculated by Cochran-Mantel-Haenszel chi-squared test on known data. Subsequently, we created a 3D GxE landscape plot of negative logarithm of the association of p-values for all the possible combinations of genetic and environmental factors with their hierarchical clustering. Thus, the GxE landscape plot is a valuable model to predict association of p-values for GxE and similarity among genotypes and environments in the context of disease pathogenesis.


BACKGROUND
GxE - Gene-environment interactions, GWAS - Genome-wide association study, MAFs - Minor allele frequencies, SNPs - Single nucleotide polymorphisms, EWAS - Environment-wide association study, FDR - False discovery rate, JPT+CHB - HapMap population of Japanese in Tokyo, Japan - Han Chinese in Beijing.
Dept of Bioclinical Informatics, Tohoku Medical Megabank Organization, Tohoku University.
Satoshi
S
Nagaie
Dept of Bioclinical Informatics, Tohoku Medical Megabank Organization, Tohoku University.
Soichi
S
Ogishima
Dept of Bioclinical Informatics, Tohoku Medical Megabank Organization, Tohoku University ; Medical IT Center, School of Medicine, Tohoku University.
Jun
J
Nakaya
Dept of Bioclinical Informatics, Tohoku Medical Megabank Organization, Tohoku University ; Dept. of Bioinformatics, Medical Research Institute, Tokyo Medical and Dental University.
Hiroshi
H
Tanaka