Computational protocol: Comparison of 2 models for gene–environment interactions: an example of simulated gene–medication interactions on systolic blood pressure in family-based data

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Protocol publication

[…] Type 2 Diabetes Genetic Exploration by Next-generation sequencing in Ethnic Samples (T2D-GENES) Consortium Project [] genotypic and GAW19 simulated phenotypic data have been described separately []. The GAW19 genotypic dosage data come from whole genome sequence variants for 20 extended Mexican American families collected as part of the San Antonio Family Studies. Imputation for missing SNP genotypes in pedigrees was conducted using a likelihood-based method implemented in MERLIN, based on the framework of available high-density genome-wide SNP data []. The GAW19 conveners simulated 200 replicates of phenotypic data based on the observed longitudinal data in the family-based sample. These data included 3 predicted deleterious coding variants in CYP3A43 with simulated gene–medication interactions in the absence of genetic main effects. We were aware that carriers of these risk variants were assigned to be nonresponsive to the simulated BP treatment effect on SBP of −6.2 mm Hg (βInt = 6.2 mm Hg). Additionally there were 984 SNPs with simulated genetic main effects for SBP explaining between less than 0.1 % and 2.78 % of the phenotypic variance. [...] To apply the med-diff approach to BP medication–stratified results (Models , ), we modeled the genetic main effect within strata of BP medication status using MMAP []. Then the Spearman rank correlation coefficient between strata for all SNPs (r, range across replicates and chromosomes: −0.13 to 0.16), magnitude, SE, and p value of the difference were estimated using EasyStrata []. The 1DF and the 2DF joint tests (shown below) have been described by Randall et al. [] and Aschard et al. []. […]

Pipeline specifications

Software tools Merlin, EasyStrata
Applications WGS analysis, GWAS
Diseases Hypertension