esSimDiffPriors: An ExpressionSet Object Storing Simulated Genotype Data

Description

An ExpressionSet object storing simulated genotype data. The minor allele frequency (MAF) of cases has different prior than that of controls.

Usage

data("esSimDiffPriors")

Arguments

Details

In this simulation, we generate additive-coded genotypes for 3 clusters of SNPs based on a mixture of 3 Bayesian hierarchical models.

In cluster $+$, the minor allele frequency (MAF) $\theta_{x+}$ of cases is greater than the MAF $\theta_{y+}$ of controls.

In cluster $0$, the MAF $\theta_{0}$ of cases is equal to the MAF of controls.

In cluster $-$, the MAF $\theta_{x-}$ of cases is smaller than the MAF $\theta_{y-}$ of controls.

The proportions of the 3 clusters of SNPs are $\pi_{+}$, $\pi_{0}$, and $\pi_{-}$, respectively.

We assume a “half-flat shape” bivariate prior for the MAF in cluster $+$ $$2h_{x+}\left(\theta_{x+}\right)h_{y+}\left(\theta_{y+}\right) I\left(\theta_{x+}>\theta_{y+}\right), $$ where $I(a)$ is hte indicator function taking value $1$ if the event $a$ is true, and value $0$ otherwise. The function $h_{x+}$ is the probability density function of the beta distribution $Beta\left(\alpha_{x+}, \beta_{x+}\right)$. The function $h_{y+}$ is the probability density function of the beta distribution $Beta\left(\alpha_{y+}, \beta_{y+}\right)$.

We assume $\theta_{0}$ has the beta prior $Beta(\alpha_0, \beta_0)$.

We also assume a “half-flat shape” bivariate prior for the MAF in cluster $-$ $$2h_{x-}\left(\theta_{x-}\right)h_{y-}\left(\theta_{y-}\right) I\left(\theta_{x-}>\theta_{y-}\right). $$ The function $h_{x-}$ is the probability density function of the beta distribution $Beta\left(\alpha_{x-}, \beta_{x-}\right)$. The function $h_{y-}$ is the probability density function of the beta distribution $Beta\left(\alpha_{y-}, \beta_{y-}\right)$.

Given a SNP, we assume Hardy-Weinberg equilibrium holds for its genotypes. That is, given MAF $\theta$, the probabilities of genotypes are $$Pr(geno=2) = \theta^2$$ $$Pr(geno=1) = 2\theta\left(1-\theta\right)$$ $$Pr(geno=0) = \left(1-\theta\right)^2$$

We also assume the genotypes $0$ (wild-type), $1$ (heterozygote), and $2$ (mutation) follows a multinomial distribution $Multinomial\left\{1, \left[ \theta^2, 2\theta\left(1-\theta\right), \left(1-\theta\right)^2 \right]\right\}$

We set the number of cases as $100$, the number of controls as $100$, and the number of SNPs as $1000$.

The hyperparameters are $\alpha_{x+}=2$, $\beta_{x+}=3$, $\alpha_{y+}=2$, $\beta_{y+}=8$, $\pi_{+}=0.1$,

$\alpha_{0}=2$, $\beta_{0}=5$, $\pi_{0}=0.8$,

$\alpha_{x-}=2$, $\beta_{x-}=8$, $\alpha_{y-}=2$, $\beta_{y-}=3$, $\pi_{-}=0.1$.

Note that when we generate MAFs from the half-flat shape bivariate priors, we might get very small MAFs or get MAFs $>0.5$. In these cased, we then delete this SNP.

So the final number of SNPs generated might be less than the initially-set number $1000$ of SNPs.

For the dataset stored in esSim, there are $838$ SNPs. $64$ SNPs are in cluster -, $708$ SNPs are in cluster $0$, and $66$ SNPs are in cluster $+$.

References

Yan X, Xing L, Su J, Zhang X, Qiu W. Model-based clustering for identifying disease-associated SNPs in case-control genome-wide association studies. Scientific Reports 9, Article number: 13686 (2019) https://www.nature.com/articles/s41598-019-50229-6.

Examples

Run this code

# NOT RUN {
data(esSimDiffPriors)
print(esSimDiffPriors)

pDat=pData(esSimDiffPriors)
print(pDat[1:2,])
print(table(pDat$memSubjs))

fDat=fData(esSimDiffPriors)
print(fDat[1:2,])
print(table(fDat$memGenes))
print(table(fDat$memGenes2))
# }

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