I just recently started using my Yubikeys (in Challenge-Response mode) w/ LUKS to unlock my drives at boot -- it's pretty neat!
On my primary system (a workstation, at home), I use the Yubikey to house my GPG keys and I use the "derived" SSH key that lives inside of it for authenticating to everything at $work. It was a bit of a PITA to get working -- points at gnome keyring -- but it works great. I have a Nano I'm about to set up the same way and just leave it in my primary laptop permanently.
What was the gist of it? I use LUKS with a pretty strong password on Fedora 25 and have a few Yubikeys I need to put to good use.
Take a look at this: https://github.com/agherzan/yubikey-full-disk-encryption