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.

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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
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article

When Pipelines Run but Coordinates Fail: A Simple Spatial Specificity Check for False Locality in post-GWAS Analysis

Hongcheng Zhu, Changzai Li, Zheng Han
Journal of Bioinformatics and Computational Biology
Genetic Associations and Epidemiology
article

When Pipelines Run but Coordinates Fail: A Simple Spatial Specificity Check for False Locality in post-GWAS Analysis

Hongcheng Zhu, Changzai Li, Zheng Han
article en

Abstract

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.

Journal of Bioinformatics and Computational Biology
Openalex Percentile: Top 5%
Genetic Associations and Epidemiology
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When Pipelines Run but Coordinates Fail: A Simple Spatial Specificity Check for False Locality in post-GWAS Analysis — Hongcheng Zhu, Changzai Li, et al. · Journal of Bioinformatics and Computational Biology (2026) | TGRS Research Map | TGRS