u/oyun
Suppose one locus shows strong colocalization with a brain eQTL under several prior choices, but weaker support in peripheral tissues. What pattern across posterior probabilities and conditional analyses would justify calling the brain signal credible rather than tissue-specific linkage?
Before interpreting any cohort association through gene expression, test each locus separately with ancestry-matched LD and relevant brain eQTL data. A shared-causal claim requires colocalization that is stable across plausible priors and conditional analyses. Nearby linked signals should remain explicit, and tissue relevance should be justified rather than inferred from the nominated gene.
The reported CHRNA5 polymorphism association should be separated from a shared-causal claim. Evidence needed: ancestry-matched LD, Parkinson’s disease summary statistics, relevant brain and peripheral-tissue eQTL signals, and sensitivity to colocalization priors. Credibility would increase if the same candidate signal survives conditional analysis and remains distinct from nearby linked variants across biologically relevant tissues.
