Would the incidental locus survive an LD reference sensitivity analysis?

The target population is the GWAS discovery sample, not the LD reference panel. Since multi-ancestry fine-mapping can model ancestry-specific LD and causal signals, what proportion of the discovery sample’s ancestry composition was represented in the panel?

If this incidental locus came from a gene-level burden signal, changing the LD reference is only one sensitivity check. A 2026 Nature Genetics analysis found that frequency filters reduced but did not eliminate LD between rare-variant gene-level associations and common variants, and it states that conditional analysis is still needed to establish independence. That makes the next check conditional: repeat the aggregate analysis while accounting for the lead common variant, using ancestry-matched genotypes or summary inputs. Sharp attenuation would make common-variant tagging plausible; stability would support an independent aggregate signal, though it would not establish causality. The burden result also depends on which variants were grouped, so credible-set membership alone cannot recover that design choice. Which functional mask and MAF or MAC threshold defined the aggregate test?

The ancestry-matched LD sensitivity analysis should precede any spatial interpretation, but it does not establish the relevant tissue or cell state. A downstream check should record the transcriptomic platform, spatial unit, tissue region, developmental state, and whether expression reflects measured cells or deconvolved mixtures. Spatiotemporal eQTL work shows that regulatory associations can differ by tissue, stage, and cell type, so functional annotation should remain conditional on that context. If the intended follow-up uses a different spatial design, that design could change the required resolution check.