{"paper_id":"e36c23b5-cb68-494d-bffd-a316fbda9673","body_text":"Abstract\nWe examined clinical, genetic, and molecular links between sleep disorders and endometriosis. Women aged 20–54 years in NHANES 2005–2006 were analyzed with survey-weighted logistic regression. Bidirectional two-sample Mendelian randomization (MR) was used to assess genetic directionality. Endometriosis-related genes were obtained from the Endometriosis eQTL analysis, whereas sleep disorder-related proteins were obtained from the sleep disorder pQTL analysis and mapped to their encoding genes. The two candidate lists were intersected by gene symbol, and shared candidates were evaluated by pathway enrichment, transcriptomic validation, machine-learning prioritization, single-cell localization, drug-gene annotation, and exploratory docking. Among 1,460 women, clinician-diagnosed sleep disorder was more common in those with endometriosis than in those without endometriosis (weighted prevalence, 13.4% vs 5.1%). In the core adjusted model, endometriosis was associated with higher odds of clinician-diagnosed sleep disorder (OR 2.64, 95% CI 1.03–6.76; P = 0.044). Forward MR suggested a modest association between genetic liability to sleep disorders and endometriosis risk (IVW OR 1.11, 95% CI 1.00–1.22; P = 0.040), whereas reverse MR provided no clear evidence for the opposite direction. Intersecting endometriosis-related eQTL genes with sleep disorder-related pQTL protein-coding genes yielded 37 shared xQTL-prioritized gene/protein candidates. Downstream analyses highlighted glucose metabolism, MAPK signaling, inflammatory pathways, and stromal-cell expression of SPARC and YEATS4. Sleep disorders and endometriosis showed convergent epidemiologic, genetic, and expression-based signals. The core clinical association remained positive after adjustment for major demographic and lifestyle covariates. The genetic and molecular findings should be interpreted as hypothesis-generating pending prospective and experimental validation.\nSimilar content being viewed by others\nData availability\nNo new datasets were generated in this study. All data analyzed are publicly available: NHANES 2005–2006 data are available from the National Health and Nutrition Examination Survey (NHANES); genome-wide association summary statistics for sleep disorders (OpenGWAS id: finn-b-SLEEP) and endometriosis (details in Supplementary Table 1) were obtained from the OpenGWAS and Finn resources; transcriptomic and single-cell RNA-seq datasets were downloaded from the Gene Expression Omnibus (GEO) (GSE4888, GSE5108, GSE6364, GSE7846, GSE37837, GSE58178, GSE120103, and GSE214411). 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JC drafted the initial manuscript. All authors participated in reviewing and editing multiple versions of the manuscript. YWY, JC and LCS supervised the study and secured project funding. All authors reviewed the manuscript.\nCorresponding author\nEthics declarations\nEthics approval and consent to participate\nThis study was a secondary analysis of de-identified, publicly available data. For the NHANES 2005–2006 component, the original NHANES protocols were approved by the National Center for Health Statistics Research Ethics Review Board, and all participants provided written informed consent. The present secondary analysis used publicly available de-identified data and therefore did not require additional institutional review board approval. Clinical trial number: not applicable.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher's Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nSupplementary Information\nBelow is the link to the electronic supplementary material.\nRights and permissions\nSpringer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.\nAbout this article\nCite this article\nShen, L., Chen, J. & Yang, Y. Systems-level genomic analyses reveal shared mechanisms underlying endometriosis and sleep disorders. Funct Integr Genomics 26, 203 (2026). https://doi.org/10.1007/s10142-026-01979-w\nReceived:\nRevised:\nAccepted:\nPublished:\nVersion of record:\nDOI: https://doi.org/10.1007/s10142-026-01979-w","source_license":"public-domain-us","license_restricted":false}