ArticleBrain and behavior2026
Peripheral lncRNA-IL1RAP Dysregulation in Schizophrenia: A Multi-Omics Bridge Between Immunity and Diagnosis.
Article in Brain and behavior, 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
backgroundSchizophrenia (SCZ) is frequently accompanied by peripheral immune dysregulation, yet robust and reproducible blood-based molecular markers remain limited.
objectiveWe sought a compact long non-coding RNA (lncRNA) signal in peripheral blood leukocytes (PBL) and examined how it aligns with immune-linked transcriptional programs and cellular compartments, using bulk RNA sequencing (RNA-seq), targeted validation, and a healthy-donor peripheral blood mononuclear cell (PBMC) single-cell reference for localization.
methodsPBL from 50 first-episode or unmedicated SCZ patients and 50 matched controls underwent RNA-seq. We performed reference-guided transcript annotation and generated lncRNA and mRNA count matrices. Differential expression was assessed with edgeR (TMM normalization). Candidate lncRNAs were prioritized using sample-level lncRNA-mRNA co-variation, followed by qRT-PCR validation in an independent cohort and evaluation with a two-feature logistic regression model using repeated 10-fold cross-validation. Pathway-scale analyses and weighted gene co-expression network analysis (WGCNA) summarized coordinated programs. Single-cell data from healthy donors were used for expression localization only, not case-control testing.
resultsWe observed a small set of dysregulated lncRNAs alongside broader mRNA changes. Two candidates at the CCR3 and IL1RAP loci (TCONS_00134168/lncRNA-CCR3 and TCONS_00138311/lncRNA-IL1RAP) showed consistent case-control directionality and were supported by qRT-PCR. The two-lncRNA model showed strong internal discrimination (AUC = 0.933) but weaker, uncertain performance in a small external qRT-PCR set (AUC = 0.656). Enrichment analyses highlighted synapse-related annotations, RNA processing/translation, and immune signaling, with recurrent involvement of IL1RAP-linked IL-1 branches. WGCNA placed lncRNA-IL1RAP and IL1RAP within diagnosis-inversely associated co-expression programs, whereas lncRNA-CCR3 showed a more transcript-specific pattern. In the healthy-reference single-cell atlas, IL1B/IL1RAP/HSF1 signals were most prominent in the monocyte/macrophage compartment.
conclusionTogether, these findings support an exploratory two-lncRNA candidate marker concept, while underscoring the need for larger multi-center validation and targeted mechanistic follow-up without implying causality.
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