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I am trying to see which predictors in my dataset are interacting with each other to see if their inclusion can improve model prediction. I followed these steps to do my analysis:

  • First I used lm on all predictors.
  • Then I used backward regression to select predictors.
  • Then I ran lm on the selected predictors.
  • Then I ran lm on the selected predictors + interacting predictors.

Here is the code:

##do full mode summary rsquared:
summary(lm(ENSG00000130943.6 ~ ., data = combine_df))$r.squared
[1] 0.9439404

##backward regression:
fullModel = lm(ENSG00000130943.6 ~ ., data = combine_df) # model with all 9 variables
nullModel = lm(ENSG00000130943.6 ~ 1, data = combine_df) # model with the intercept only
backward.model <- stepAIC(fullModel, # start with a model containing all the variables
                direction = 'backward', # run backward selection
                scope = list(upper = fullModel, # the maximum to consider is a model with all variables
                             lower = nullModel), # the minimum to consider is a model with no variables
                trace = 0) # do not show the step-by-step process of model selection


summary(backward.model)$r.squared
[1] 0.9377306

##now in backward model try to do with interaction term:
summary(lm(formula = ENSG00000130943.6 ~ rs1 + rs3 + rs4 + rs6 + rs7 + 
       rs8 + rs9 + rs10 + rs11 + rs12 + rs14 + rs18 + rs20 + rs25 + 
        rs26 + rs27 + rs40 + rs44 + rs45 + rs46 + rs47 + rs48 + rs49 + 
       rs50 + rs53 + rs54 + rs57 + rs58 + rs59 + rs60 + rs63 + rs64 + 
       rs65 + rs68 + rs69 + rs70 + rs71 + rs72 + rs76 + rs78 + rs80 + 
       rs81 + rs82 + rs83 + rs85 + rs88 + rs89 + rs93 + rs98 + rs102 + 
      rs105 + rs107 + rs109 + rs110 + rs111 + rs112 + rs117 + rs118 + 
        rs121 + rs122 + rs123 + rs124 + rs125 + rs126 + rs127 + rs128+rs128*rs123,
   data = combine_df))$r.squared
[1] 0.9388159

I then did an ANOVA test on predictors that might interact and plotted their interactions. The ANOVA test gives a p-value of 0.89 for interacting predictors, which is not good. Then I plotted an interaction plot which does show an interaction. enter image description here

summary(anova)
             Df Sum Sq Mean Sq F value  Pr(>F)   
rs128         1   3.59   3.591   9.993 0.00181 **
rs123         1   3.85   3.852  10.719 0.00125 **
rs128:rs123   1   0.01   0.006   0.017 0.89631   
Residuals   201  72.24   0.359                   
---
Signif. codes:  0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
> 
> anova
Call:
   aov(formula = ENSG00000130943.6 ~ rs128 * rs123, data = combine_df)

Terms:
                   rs128    rs123 rs128:rs123 Residuals
Sum of Squares   3.59130  3.85217     0.00612  72.23577
Deg. of Freedom        1        1           1       201

I wanted to ask whether this analysis is correct in terms of including interacting terms as well as how to see all the interacting terms when number of predictors are large. I selected rs128 and rs123 as interacting since it shows *** during backward regression for these two variables. I basically want to further rank or select predictors whose presence can improve model performance. I will be highly grateful if someone can provide more guidance on this since I am new to regression analysis. My dataset for reference:

dput(combine_df[1:5,1:5])
structure(list(ENSG00000130943.6 = c(-0.0814098051060948, 0.206379671030366, 
0.321031350919992, 0.513621983895094, 0.659905091586951), rs1 = c(2L, 
0L, 1L, 0L, 0L), rs2 = c(2L, 0L, 1L, 0L, 0L), rs3 = c(2L, 0L, 
1L, 1L, 1L), rs4 = c(0L, 0L, 0L, 0L, 0L)), row.names = c("GTEX-1117F", 
"GTEX-111FC", "GTEX-1128S", "GTEX-117XS", "GTEX-1192X"), class = "data.frame")
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1 Answer 1

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Overfitting Regressions

The first thing I noticed when I read this was the absurd number of predictors included in your regression. Without any rhyme or reason behind this, it is no wonder the $R_2$ is incredibly high...this regression seems to be, by definition, a case of overfitting. I would have a hard time even finding this regression interpretable, but perhaps you could provide more information about what these rs variables are. It also seems odd to me that despite having more than 100 predictors, you contrarily only include a single interaction. What is the reasoning behind this? It would be helpful to know what brought you to doing this in the first place. If this regression is meant to explain some hypothetical relationship between the predictors and outcome, it should be clear what each variable contributes before the regression is conducted.

Alternatives

I'm going to make a giant assumption that these variables are all highly related to each other in some way. That presents its own problems if you have issues with, say, multicollinearity. If that is the case, you could consider some type of data reduction to make this model more interpretable. For example, if your predictors are all on the same scale and measure very similar things, you could simply create a composite that represents whatever theoretical factor is influencing your outcome. Of course this would also require other steps like ensuring the items are reliable in some way. You could also consider something like a principal components regression. Either of these techniques would be more parsimonious and useful than a model with 128 main effects plus an interaction.

Additional Notes

At some point you were using p-values as approximations of whether or not certain interactions should exist in your model. Don't. With this amount of predictors being included in your regression, there's no telling what chance findings you can come up with by doing this. You mentioned not being far into regression analysis, and that you are using R. I highly recommend going through Regression and Other Stories. It will teach you a lot about regression and may provide you with better insight on how to work with these statistical techniques.

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