Hello, I'm new to GenABEL and ProbABEL. I'm using ProbABEL at the moment, however, I'm a little confused about the output.
Say for example I'm fitting the following model:
y ~ m + cov1 + cov2 + E + SNP + SNP*E  (model 1)
What I'm really interested in is testing if the SNP*E is statistically significant. Normally, I would do a likelihood ratio test by subtracting the 2 log likelihoods of the full model (model 1) with a reduced model (model 2 below) to obtain a chisquare statistic with 1 degree of freedom.
y ~ m + cov1 + cov2 + E + SNP  (model 2)
I fit the full model (model 1). The output for ProbABEL provides a chi2_SNP statistic. I'm assuming that this is the chisquared statistic from the LRT comparing the full model as I fit above with a null (no covariate) model (NOT to be confused with the reduced model)... is this correct? Verification of this would be helpful.
So if I wanted a pvalue for the SNP*E interaction term comparing nested models (full  reduced) to get the LRT, how would I go about getting it with ProbABEL? (other than simply doing beta_SNP*E/se_SNP*E, which would be equivalent to doing a wald test)
Is it appropriate to fit model 1 then model 2 and then subtract the chi2_SNP values to get the SNP*E chi2 for 1 degree of freedom?
Thank you for your help.
Understanding probabel GxE interaction output
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 Posts: 2
 Joined: Thu May 21, 2015 8:13 pm
Re: Understanding probabel GxE interaction output
I have the same question.
I hope to get an significant p value for G*E term. How to get that p value. And coefficients for that interaction term.
Thanks!
I hope to get an significant p value for G*E term. How to get that p value. And coefficients for that interaction term.
Thanks!

 Posts: 2
 Joined: Thu May 21, 2015 8:13 pm
Re: Understanding probabel GxE interaction output
Hello,
You can obtain the pvalue for the interaction term by dividing the SNPxcovariate_interaction_beta by the SNPxcovariate_interaction_standard_error. This gives you a zscore which you can convert into pvalue using R doing something like this for example: 2*pnorm(abs(zscore). This should give you a twosided pvalue for interaction.
My original question however has not been answered at all, which is: What is the chi2_SNP test statistic for (in the event we run an interaction analysis):
a) the SNP
b) the interaction term of the SNP and the covariate
c) the whole model in question compared to the nullmodel.
Help with this query would be greatly appreciated.
Thank you much.
You can obtain the pvalue for the interaction term by dividing the SNPxcovariate_interaction_beta by the SNPxcovariate_interaction_standard_error. This gives you a zscore which you can convert into pvalue using R doing something like this for example: 2*pnorm(abs(zscore). This should give you a twosided pvalue for interaction.
My original question however has not been answered at all, which is: What is the chi2_SNP test statistic for (in the event we run an interaction analysis):
a) the SNP
b) the interaction term of the SNP and the covariate
c) the whole model in question compared to the nullmodel.
Help with this query would be greatly appreciated.
Thank you much.
Re: Understanding probabel GxE interaction output
I have verified the ProbABEL results manually in R using the imputed dosages. It seems as though when running palinear with an interaction term (GxE), the chi2_SNP test statistic is a 2df statistic from Likelihood Ratio Test. The full model is containing all 3 terms G, E, and GxE (plus the covariates), and the null model only contains E (with the same covariates). So it considers the "null model" to be without both genetic terms (G and GxE). I'll denote this as the Likelihood Ratio L(GxE)/L(E) which asymptotically approaches a 2df chisquare statistic.
I think if we want Pvalues for the individual terms, we will need to perform either
1. A Wald Test using the coefficient and the SE
2. Another ProbABEL run without the GxE term to obtain a chi2_SNP statistic representing the 1df L(G,E)/L(E) statistic. This way we can obtain, say, L(GxE) /L(G,E) chisqstatistic which is also 1df, for a test of the interaction term by itself.
Hope this is helpful!
I think if we want Pvalues for the individual terms, we will need to perform either
1. A Wald Test using the coefficient and the SE
2. Another ProbABEL run without the GxE term to obtain a chi2_SNP statistic representing the 1df L(G,E)/L(E) statistic. This way we can obtain, say, L(GxE) /L(G,E) chisqstatistic which is also 1df, for a test of the interaction term by itself.
Hope this is helpful!
Re: Understanding probabel GxE interaction output
Thanks Nick! I hadn't had the time yet to check the code before answering.
I'll update the manual to make this more explicit.
I'll update the manual to make this more explicit.

Lennart Karssen
PolyOmica
The Netherlands

Lennart Karssen
PolyOmica
The Netherlands

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