ArticleCureus2026
Opposing Molecular Programs in Obsessive-Compulsive Disorder and Hoarding: Transcriptome-Wide Association Studies Reveal Distinct Senescence, Complement, and Metabolic Signatures.
Article in Cureus, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
BACKGROUND AND
objectiveObsessive-compulsive disorder (OCD) and hoarding disorder often co-occur but differ in onset, course, symptoms, and treatment response. This study compared diagnosis-based OCD genetic liability with hoarding-symptom liability, rather than direct expression differences between diagnosed patient groups.
methodsLarge-scale OCD and hoarding genome-wide association study (GWAS) summary statistics were integrated with brain expression quantitative trait loci (eQTL) reference panels using a transcriptome-wide association approach. Gene-set enrichment was assessed across six brain regions with Stouffer's Z-score meta-analysis, empirical permutation testing, paired phenotype comparisons, and exploratory gene-level analyses. Transcriptome-wide association studies (TWAS) Z-scores were interpreted as genetically predicted expression associated with trait liability, not measured tissue expression.
resultsThe OCD liability showed positive intrinsic apoptosis enrichment (Z = +5.707; permutation p = 0.005899), positive complement enrichment (Z = +4.932; p = 0.0164), and a negative synapse-pruning profile (Z = -4.802; p = 0.0178). Hoarding-symptom liability showed a more positive cellular-senescence profile than OCD (Mann-Whitney U p = 0.008861; local false discovery rate (FDR) = 0.008861). Nicotinamide adenine dinucleotide (NAD)/sirtuin (SIRT) findings were directionally hoarding-skewed but exploratory.
conclusionsThese findings suggest divergent, hypothesis-generating molecular signatures, namely senescence/NAD-biased aging signals in hoarding and apoptosis, complement-pruning, and metabolic-reward dysregulation in OCD. The TWAS findings require validation with colocalization, fine-mapping, and functional studies.
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