Would you do this:

In reference to your question; you may wnat to call your friend.

or

In reference to your questions: you may want to call your friend.

You should definitely use a comma. A semicolon (;) is wrong as is a colon. (:).

So, it should be:

"In reference to your questions, you may want to call your friend."

Here's a quick lesson on comma after a sentence introduction.