The first discard is the most over-determined move in the hand and the easiest one to overthink. The objective is to release a card that costs as little as possible to lose. A high-value card that does not belong to any plausible meld is the obvious candidate, but two refinements matter.
First, the open pile is a record of what every other player has chosen not to keep. A card that has already been discarded twice is unlikely to be the missing piece of anyone's hand. Releasing it costs you whatever the hand might have built around it, but it costs very little because the rest of the table has already signalled that they did not want it. The odds page explains why a doubled discard is also the cheapest card to release in information terms.
Second, a wildcard is not always the safest hold. A joker that does not fill a gap in a near-run is a wasted card: it counts towards the thirteen, it cannot form a pure sequence, and at show time it will sit in the dead zone unless it pairs with a sequence of its own. Releasing a wildcard for a high card that fits a real run is sometimes the better move, particularly in the early draw when the closed pile still holds most of the unseen cards.
What to discard first
Discard in this order. First, high-value unmatched cards that have already appeared in the open pile. Second, a wildcard that does not fill a gap. Third, the odd card out of a pair when a run is one card closer than a set. Hold a wildcard whenever it completes a near-run of three cards of the same suit, and hold a near-run of four even when a high card sits beside it.