Varroa mites are a vector for diseases and fungus and most likely the distal cause of most of the dying colonies. If they are not aggressively managed, they eventually lead to the death or absconding of almost every colony.
My preference is to alternate "natural" thymol/oxalic treatments with Apivar. You can really see the reduction in virus laden malformed bees in a hive turnover (~6 weeks). Apivar treatment lasts a full year, but I'd rather not develop resistance (don't leave strips in the hive longer than 8 weeks!) so alternate years. The best time I've seen for treatment is right before large population booms (since there are fewer mites in brood). That usually means early winter after supers are removed, or after a queen swarm leaves in late winter/early spring.
One major challenge to resistant queens is that they tend to be more aggressive and their resistance is diluted unless you requeen (resistant) every year or two due to interbreeding with local non-resistant drones.
I'm not worried about the amount of honey.
https://www.youtube.com/watch?v=tuJlgzcQWAg
It's an hour long and very informative. The research seems well backed up.
The problem with the genetics is that it's extremely hard to maintain continuity of a colony beyond a few years because eventually they need to requeen. Those future queens are made from a variety of contributions of other gene lines due to the way the mating happens.