Peripheral origins of genetic neurological disease: a mechanistic classification and clinical implications

Supporting data, code, specifications and audit for the manuscript “Peripheral origins of genetic neurological disease: a mechanistic classification and clinical implications” (Journal of Medical Genetics, manuscript jmg-2026-112058). The study classifies gene–disease mechanisms by the site of the initiating defect, distinguishing nervous-system-intrinsic disease from systemic disease that reaches the brain through a peripheral organ and a disturbed mediator. A transcriptional specificity index derived from Human Phenotype Ontology annotations and GTEx expression data is used to rank candidates, and its limitations are assessed against selected controls, pathway-defined groups and a second expression resource. Selected candidate routes are connected to published neurological intervention evidence. The archive contains derived data tables and per-study outputs, the analysis and figure code, the hashed specification records and their addenda, an independent downstream audit, and scripts that retrieve the public primary inputs, verify their checksums and reproduce both the table 1 control values and the 4,171-gene denominator reported in the manuscript. A SHA-256 manifest covers the archived files. Primary inputs are cited rather than redistributed. The GTEx V10 median gene-level TPM matrix (GTEx_Analysis_v10_RNASeQCv2.4.2_gene_median_tpm.gct.gz, SHA-256 b951fd32aae5cad48435026e07225860596a411a75efd0519e00f330b7a98294) is available from the GTEx Portal. The Human Phenotype Ontology 2026-09-01 release (hp.obo, SHA-256 93dace952fcb3ec4728818857f6ba76bc2d5312f4d83266519b8694b8e798f22; phenotype_to_genes.txt, SHA-256 7b7a0f71b7c6d2bdfff3d6f075c567c56d668495a4fd80f0bc35f690a221d00b) is available from the Human Phenotype Ontology project repository. Known limitations: a referenced control-pool file and an environment lockfile were not retained, so the selection of matched comparators and the exact software environment cannot be reconstructed from this deposit, and a complete end-to-end rerun is not yet possible. The annotation-provenance analysis is post-hoc and is labelled as such throughout. These limitations are stated in the manuscript and itemised in its online supplemental material.