I suggest going for retrograde and hounded individual for maximum charateristics, lone genius is bad because of the slow leveling, and big boned only gives you 2 more characteristics to work with, whereas both Retrograde and Hounded Individual give you 3, 6 combined. Hounded individual is bad if youre planning to take companions, but 3 extra characteristics will be much more useful. You can always complete their quests once youve essentially finished the rest of the game, then the debuffs wont really matter.