No one can determine the effect certain threats will cause, but some "popular" threats are:

• Extreme government regulation.
• Bitcoin losing to a competitor coin.
• Technical attacks, including attacks on protocol (51% attack) or attacks on cryptography.
• Intentional market manipulation to crash the price.

Some factors that can drive these events to be more likely to occur or enable them are:

• Unresolved technical issues, such as blockchain bloat, or transaction limits within blocks.
• End of or diminishing block rewards causing people to abandon mining.
• Increased centralization for whatever reason (advanced technology, zero power costs, etc.)