Where is the best place to add Relationships to Custom Modules.

I need to add a new relationship to a Custom Module, which was not originally built with Module Builder, should I add the relationship via Studio or the Module Builder?

If I have a module that shows to be available in the Module Builder but was not originally built there, what will happen if I begin to add relationships/fields/update layouts? Do I risk corrupting data that is currently apart of this module if I don't do things in a certain order?