To Brucey's list of causes of fatigue, I would add insufficiently tensioned spokes, which are more common on cheaper bikes and on machine built wheels. If you do start building your own wheels, a good tensiometer will help you avoid this problem.
needless to say if the overall tension is insufficient in a rear wheel, it is the NDS spokes that are liable to break first, not the DS.
'Insufficient tension' might be defined by the spokes going slack in service; this can cause
a) the nipples to back out
b) the spokes to rub at the crossings (which you can often hear)
c) the spokes to fret in the hub drilling
d) the spokes to flex abnormally (in compression, eg by buckling) and suffer accelerated fatigue
If you are wondering how close you are sailing to the wind with a dished (rear) wheel design, you can build it with good lubricant on the nipples and ride it for a bit. If the NDS nipples start to back out PDQ (within the first hundred miles or so) you may well have something that is intrinsically unsuitable on your hands (for the service loads encountered). If it still happens but it isn't so swift/severe, it may be within the scope of being fixable using threadlock on the NDS nipples.
Needless to say most modern wheelsets with low spoke counts won't work without threadlock on the nipples.
cheers