The gxeRC R package computes power analyses for gene by environment interactions of both rare and common variants.
install.packages("devtools") # devtools must be installed first
devtools::install_github("SharonLutz/gxeRC")
For n subjects, the number of SNPs X inputted by the user (input: nSNP) are generated from binomial distributions with minor allele frequency specified by the user (input: MAF). The environmental factor Z is generated from a normal distribution with mean and variance inputted by the user. The outcome Y is generated from a normal distribution with mean as follows:
E[Y] = β0 + βz Z + ∑j βx Xj + βI ∑j Xj Z
for j=1,...,k where k= the number of SNPs.
See the manpage for more detail regarding the input of the gxeRC function.
library(gxeRC)
?gxeRC # For details on this function
For 5,000 subjects, 3 SNPs X with MAF of 0.05, 0.01, and 0.005, respectively, and a normally distributed environmental factor Z, we generated the power for the SNP by environment interaction on the outcome Y for each SNP independently and for the joint interaction using the following commands.
library(gxeRC)
gxeRC(n = 5000, nSNP = 3, MAF = c(0.05, 0.01, 0.005), betaX = c(0.25, 0.25, 0.25),
betaI = c(0, 0.05, 0.1),zMu = 0, zVar = 1, yVar = 1, nSim = 1000, alpha = 0.05)
For this example, we get the following matrix and corresponding plot which output the type 1 error rate (row 1 of the matrix) and the power (row 2 and 3 of the matrix) to detect the SNP by environment interaction on the outcome. We can see from the plot below that we have the most power in this scenario when the SNP by environment interaction is tested for all 3 SNPs instead of for each SNP individually.
lmX1 lmX2 lmX3 lmAll
[1,] 0.016 0.015 0.020 0.052
[2,] 0.095 0.030 0.017 0.154
[3,] 0.439 0.091 0.045 0.578
The power analysis used here was implemented in the following manuscript:
Lutz SM, Frederiksen B, Begum F, Cho MH, Hobbs B, McDonald ML, Parker MM, DeMeo DL, Jiang L, Eringher M, Young K, Foreman MG, Kinney GL, Make BJ, Lomas DA, Bakke P, Gulsvik A, Crapo JD, Silverman EK, Beaty TH, Hokanson JE. (2019) Common and Rare Variants Genetic Association Analysis of Cigarettes Per Day Among Ever Smokers in COPD Cases and Controls. NTR. 21(6):714-722.
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