When Pipelines Run but Coordinates Fail: A Simple Spatial Specificity Check for False Locality in post-GWAS Analysis
Some post-GWAS analysis software can run to completion without reporting an error while producing results that are not biologically valid. We call this failure false locality: a result appears to be local to a gene or protein because it was produced from a regional window, but the window or its metadata points to the wrong genomic address. We identify three mechanisms. First, genome-build address mismatch occurs when GRCh38 protein-QTL coordinates are used with GRCh37 outcome files; in our 91-sentinel audit, 66 coordinates moved by more than 100 kb and 54 moved by more than 200 kb after remapping. Second, non-specific regional noise occurs when significant P values persist after the analysis window is deliberately moved to a zero-overlap variant set. Third, location-label blindness occurs when software returns the same output after the declared coordinate label is changed while the SNP table is unchanged; in an official SMR/HEIDI CXCL10 test, the top SNP, SMR P value, and HEIDI P value remained identical across correct, wrong, and shifted labels. We propose a simple Change Test: a result should not be treated as local evidence unless the numerical output changes, weakens, or disappears when the analysis window or coordinate label is intentionally moved to a biologically wrong location. This standard turns software execution from a passive success signal into an explicit spatial-specificity check.
Authors
- Hongcheng Zhu (ORCID: https://orcid.org/0000-0001-7444-5123)
- Changzai Li
- Zheng Han
Publication Details
- Journal
- Journal of Bioinformatics and Computational Biology
- Published
- 2026-05-22
- DOI
- https://doi.org/10.1142/s0219720026710034
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00