{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:06:51Z","timestamp":1788930411191,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Science and Technology Program","award":["JCYJ20250604150048016"],"award-info":[{"award-number":["JCYJ20250604150048016"]}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20240813152313019"],"award-info":[{"award-number":["JCYJ20240813152313019"]}]},{"DOI":"10.13039\/501100001809","name":"The Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82374531"],"award-info":[{"award-number":["82374531"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen High-level Hospital Construction Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>The co-occurrence of liver cirrhosis (LC) and heart failure (HF) poses considerable clinical challenges, yet the cellular and molecular determinants of this comorbidity remain poorly characterized. To address this, we developed an integrative multi-omics pipeline encompassing GWAS meta-analysis, gsMap-based spatial transcriptomic projection, GeneEnrich functional annotation, single-cell atlas construction, seismicGWAS and ECLIPSER cell-type scoring, eCAVIAR and fastenloc colocalization, hdWGCNA network inference, scTenifoldKnk in silico gene perturbation, and GCTA-COJO fine-mapping. Quality-controlled meta-analysis yielded 12,347,758 and 9,256,862 variant-level associations for LC and HF, respectively. Spatial projection confirmed preferential enrichment of disease signals within embryonic hepatic and cardiac compartments. Pathway analyses disclosed that LC-linked loci were concentrated in lipid metabolic programs, whereas HF-linked loci implicated mitochondrial bioenergetics and lysosomal degradation. At the cellular level, endothelial cells emerged as the dominant HF-associated population. Convergent evidence from five orthogonal algorithms pinpointed CRIM1 as the sole robustly supported shared gene, selectively enriched in HF endothelial cells; virtual perturbation further identified LCP1 and PTPRC as downstream regulatory nodes. Fine-mapping of the chromosome 2 locus harboring rs12476437 revealed multiple statistically independent signals in the vicinity of CRIM1. Collectively, these findings computationally prioritize the endothelial\u2013CRIM1 axis as a previously unappreciated candidate mechanistic bridge between LC and HF requiring experimental validation.<\/jats:p>","DOI":"10.3390\/ijms27177936","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"7936","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Deciphering the Genetic Underpinnings of Liver Cirrhosis\u2013Heart Failure Comorbidity Through Multi-Omics: CRIM1 as a Key Endothelial Mediator"],"prefix":"10.3390","volume":"27","author":[{"given":"Ruiqi","family":"Zhao","sequence":"first","affiliation":[{"name":"The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen 518033, 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