## Problem 027 — rank:55

**Title:** Causal non-coding variants

**Added binding assumptions (LaTeX):**

```latex
A single-variant contrast must state what happens to the other candidates: fix their haplotype at $u_{-v}=u^0_{-v}$ or average over a declared distribution. These estimands differ under interactions. Natural variant comparisons require confounding assumptions beyond matched backgrounds. Perturbing a proposed mediator is evidence for a mediated pathway only under an explicitly defined mediation estimand and the required intervention assumptions.
```

**Direct edits:** 0. **Fresh external checks:** None; supplied sources retained as provenance.