The most major threat to the human race other than I-slam is probably genetic entropy.
That process is inevitable, making it not a "threat" but a certain destiny.
Inbreeding increases the downward slope to "poodle-ization" of the population. That is, when one confines the genetic pool, one ends up with a worthless dog that is weak, sick and high maintenance at least when compared to a mutt (that with higher genetic diversity).
Curiously, those who like to tinker with human genetics with the aim of creating a master race for some reason like to breed out genetic information so we end up with "poodles". On the other hand, one could argue that the raping and pillaging (mostly the raping) of the population by invading foreign armies actually decreases the slope of genetic entropy making for hardier progeny. This could be one of those extremly rare good "unintended consequences" of UN Peace keeping missions into the third world.
According to Greco-Roman literature at least the world was somehow or other protected from such problems in recent prehistoric time. We no longer are, and just getting rid of I-slam and inbreeding won’t fix the problem. We’re capable of solving this one and we need to.