Hi,

I ran a multiple linear regression to check the relationship between methylation and cortisol.

When I extract the results I have a significant site (p-value) but the coefficients are really small. I am having trouble interpreting the results. Would that mean that this has no practical significance (cause the estimates are very small)?

Or do I need to standardize the independent variable (x = cortisol) that I have used? (if I have to standardize, can you please recommend how to do it via limma)

```
coef AveExpr t P.Value adj.P.Val
#cg20460797 -0.005752230 -7.026308 -6.440652 3.950537e-09 0.003194222
#cg11409463 0.002670708 2.8029989 5.956008 3.568092e-08 0.02884995
#cg01061425 -0.003401554 -6.637181 -5.405267 4.260207e-07 0.125154865
```

Thank you!

It means 1) you performed a lot of tests (looking at adjusted pvals) 2) you have a large sample

Small coefficients (with considerable variability) make no practical sense if taken into account without other methylation markers. But taken all together they may provide a powerful answer to your problem (eg PRS scores for genomic markers)

0.005 is not that small given the beta values are from 0 to 1

Thankyou for your reply. I understand. I was a bit worried that I might have to standardize the variable after I have run the regression. I do not have a very large sample size though but did see some effect. Thank you!