{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T13:17:02Z","timestamp":1793798222629,"version":"4.6.1"},"reference-count":67,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01HL146751"],"award-info":[{"award-number":["R01HL146751"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01DK107859"],"award-info":[{"award-number":["R01DK107859"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Insomnia is a prevalent sleep disorder with growing evidence implicating immune and inflammatory processes. Elevated C-reactive protein (CRP), a marker of systemic inflammation, is frequently observed in individuals with poor sleep, yet the genetic basis of this relationship remains unclear. This study aims to characterize the shared genetic architecture between insomnia and CRP using large-scale genomic data. CRP levels were significantly elevated in 130,\u2009611 individuals with insomnia compared with 327,\u2009375 controls in the UK Biobank. Genome-wide genetic correlation, pleiotropic analysis, colocalization, Mendelian randomization (MR), and functional annotation were used to characterize shared genetic architecture and biological pathways. Insomnia and CRP showed a significant positive genetic correlation. We identified 125 pleiotropic loci jointly associated with insomnia and CRP. Functional annotation implicated chromatin organization and nucleosome assembly, while pathway analyses highlighted immune signaling, cellular senescence, and programmed cell death. Colocalization analysis provided support for shared causal variants at six loci in or near APOE, HLA-B, NLGN1, AK5\/DNAJB4, FAM114A2\/GRIA1, and SATB1. Bidirectional MR provided stronger evidence for a directional relationship from insomnia liability to elevated CRP than in the reverse direction. This study uncovers shared genetic mechanisms linking insomnia and systemic inflammation. The directional genetic relationship from insomnia liability to elevated CRP suggests that sleep dysfunction may contribute to inflammatory processes.<\/jats:p>\n                  <jats:p>Statement of Significance This study demonstrates that insomnia is not only associated with inflammation but may actively drive it, supported by genetic evidence and shared causal variants. By identifying loci that jointly influence sleep and immune processes, this work reveals convergence between neural regulation and systemic inflammation. The implicated genes highlight coordinated roles for synaptic function, immune signaling, cellular stress responses, and chromatin regulation, offering a more integrated view of sleep-immune interactions. Our findings move beyond prior observational links to pinpoint specific genomic regions that clarify how sleep disruption may contribute to inflammatory disease risk.<\/jats:p>","DOI":"10.1093\/sleep\/zsag254","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:46:19Z","timestamp":1791978379000},"source":"Crossref","is-referenced-by-count":1,"title":["Genetic pleiotropy highlights immune mechanisms that link insomnia and C-reactive protein"],"prefix":"10.1093","author":[{"given":"Farah","family":"Abou Daya","sequence":"first","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital , Boston, MA 02114 ,","place":["United States"]},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, MA 02114 ,","place":["United States"]},{"name":"Department of Anesthesiology, Massachusetts General Hospital, Mass General Brigham and Harvard Medical School , Boston, MA 02114 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