Using which Outs? - are you using the "official"/easier Out 1 4CM or the Out 2 L/R method?
I'm wondering if your Out1 is up too high for the Return to the FX loop.
Also, check your Boost/Pad on Out 2 in settings (I/O Audio) - make sure that is as close to 0 as possible.
The Connections piece in the manual for the 4CM example is quite good.
I however, just use the OUT2 L/R method - ok, not in the manual but found quite easily
HERE - that gives Unity to both Amp In and FX Return which gives your amp the best chance of not hissing like a gas leak.....