{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T18:51:42Z","timestamp":1791312702005,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.pgen.1012328","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000}}],"reference-count":88,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National institute of mental health","doi-asserted-by":"publisher","award":["NIMH Grant R01MH120219"],"award-info":[{"award-number":["NIMH Grant R01MH120219"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["NIMH grant T32 MH016880"],"award-info":[{"award-number":["NIMH grant T32 MH016880"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["NIMH grant T32 MH016880"],"award-info":[{"award-number":["NIMH grant T32 MH016880"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["NIA Grant R01AG073593"],"award-info":[{"award-number":["NIA Grant R01AG073593"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["U01AG083829"],"award-info":[{"award-number":["U01AG083829"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>This study explored the genetic links between 11 immune-mediated diseases and 13 psychiatric disorders, addressing the limited understanding of the underlying biological mechanisms linking these illnesses. Utilizing genomic structural equation modeling, we investigated whether the genetic liability for 14 immune markers (e.g., C-reactive protein [CRP], interleukin-6 [IL-6]) mediated associations between latent genomic factors of immune-mediated diseases (e.g., autoimmune) and psychiatric disorders (e.g., internalizing). While the literature extensively describes the psychiatric relevance of CRP, results indicated this is better explained by its biological precursor, IL-6. This is evidenced by highly attenuated associations of psychiatric traits with CRP when accounting for overlapping signal of IL6. Overall, the genetic liability of six immune markers significantly mediated 11 psychiatric-immune disease genetic relationships. For example, IL-6 mediated 60% of the genetic link between an internalizing factor and Crohn\u2019s disease. Identified markers often evinced mediating effects for multiple disorder clusters and many immune-psychiatric relationships were mediated by multiple markers. At the same time, highlighting their diagnostic relevance, only a subset of examined immune markers were significant mediators. These findings provide mechanistic insight by pinpointing the immune markers that may be most critical to the psychiatric-immune disease link, which notably did not include CRP.<\/jats:p>","DOI":"10.1371\/journal.pgen.1012328","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:41:51Z","timestamp":1790790111000},"page":"e1012328","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune markers mediate genetic relationships between immune diseases and psychiatric disorders"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6594-0587","authenticated-orcid":true,"given":"Sophie","family":"Breunig","sequence":"first","affiliation":[{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Institute for Behavioral Genetics"]},{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Department of Psychology and Neuroscience"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen M.","family":"Kelly","sequence":"additional","affiliation":[{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Institute for Behavioral Genetics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas S.","family":"Schaffer","sequence":"additional","affiliation":[{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Institute for Behavioral Genetics"]},{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Department of Psychology and Neuroscience"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy M.","family":"Lawrence","sequence":"additional","affiliation":[{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Institute for Behavioral Genetics"]},{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Department of Psychology and Neuroscience"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younga Heather","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Massachusetts General Hospital","place":["Boston, Massachusetts, United States of America"],"department":["Psychiatric and Neurodevelopmental Genetics Unit"]},{"name":"Harvard Medical School","place":["Boston, Massachusetts, United States of America"],"department":["Department of Psychiatry"]},{"name":"Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard","place":["Cambridge, Massachusetts, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth W.","family":"Karlson","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Brigham","place":["Boston, Massachusetts, United States of America"]},{"name":"Brigham and Women\u2019s Hospital, Harvard Medical School","place":["Boston, Massachusetts, United States of America"],"department":["Department of Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew D.","family":"Grotzinger","sequence":"additional","affiliation":[{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Institute for Behavioral Genetics"]},{"name":"University of Colorado Boulder","place":["Boulder, Colorado, United States of America"],"department":["Department of Psychology and Neuroscience"]},{"name":"Memorial University","place":["St. John\u2019s, Newfoundland and Labrador, Canada"],"department":["Department of Psychology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"pgen.1012328.ref001","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1007\/s00439-015-1596-8","article-title":"Pervasive pleiotropy between psychiatric disorders and immune disorders revealed by integrative analysis of multiple GWAS","volume":"134","author":"Q Wang","year":"2015","journal-title":"Hum Genet"},{"key":"pgen.1012328.ref002","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3389\/fpsyt.2019.00131","article-title":"Autoimmune diseases and psychotic disorders","volume":"10","author":"R Jeppesen","year":"2019","journal-title":"Front Psychiatry"},{"issue":"4","key":"pgen.1012328.ref003","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/imm.13597","article-title":"An immunogenetic investigation of 30 autoimmune and autoinflammatory diseases and their links to psychiatric disorders in a nationwide sample","volume":"168","author":"R Nudel","year":"2023","journal-title":"Immunology"},{"issue":"1","key":"pgen.1012328.ref004","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/s41398-025-03470-9","article-title":"Examining the genetic links between clusters of immune-mediated diseases and psychiatric disorders","volume":"15","author":"S Breunig","year":"2025","journal-title":"Transl Psychiatry"},{"issue":"20","key":"pgen.1012328.ref005","doi-asserted-by":"crossref","first-page":"3498","DOI":"10.1093\/hmg\/ddz145","article-title":"Cross-disorder analysis of schizophrenia and 19 immune-mediated diseases identifies shared genetic risk","volume":"28","author":"Schizophrenia Working Group of the Psychiatric Genomics Consortium","year":"2019","journal-title":"Hum Mol Genet"},{"key":"pgen.1012328.ref006","first-page":"1","article-title":"Shared genetic basis and causality between schizophrenia and inflammatory bowel disease: Evidence from a comprehensive genetic analysis","author":"J Wang","year":"2024","journal-title":"Psychol Med"},{"key":"pgen.1012328.ref007","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jad.2023.12.042","article-title":"Genetic correlation, shared loci, but no causality between bipolar disorder and inflammatory bowel disease: A genome-wide pleiotropic analysis","volume":"348","author":"B-R Wang","year":"2024","journal-title":"J Affect Disord"},{"issue":"20","key":"pgen.1012328.ref008","doi-asserted-by":"crossref","first-page":"11241","DOI":"10.3390\/ijms222011241","article-title":"Autoinflammatory diseases and cytokine storms\u2014Imbalances of innate and adaptative immunity","volume":"22","author":"A Marcuzzi","year":"2021","journal-title":"IJMS"},{"issue":"2","key":"pgen.1012328.ref009","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.cyto.2010.02.014","article-title":"Comparative analysis of cytokine profiles in autoinflammatory and autoimmune conditions","volume":"50","author":"G Manukyan","year":"2010","journal-title":"Cytokine"},{"issue":"1","key":"pgen.1012328.ref010","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.autrev.2012.07.018","article-title":"Autoinflammation and autoimmunity: Bridging the divide","volume":"12","author":"A Doria","year":"2012","journal-title":"Autoimmun Rev"},{"key":"pgen.1012328.ref011","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/03946320140270S101","article-title":"The role of tumour necrosis factor in the pathogenesis of immune-mediated diseases","volume":"27","author":"C Blandizzi","year":"2014","journal-title":"Int J Immunopathol Pharmacol"},{"issue":"2","key":"pgen.1012328.ref012","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1097\/PSY.0b013e3181907c1b","article-title":"Associations of depression with C-reactive protein, IL-1, and IL-6: A meta-analysis","volume":"71","author":"MB Howren","year":"2009","journal-title":"Psychosom Med"},{"key":"pgen.1012328.ref013","doi-asserted-by":"crossref","first-page":"1338083","DOI":"10.3389\/fimmu.2023.1338083","article-title":"Causal role of immune cells in generalized anxiety disorder: Mendelian randomization study","volume":"14","author":"Z Ma","year":"2024","journal-title":"Front Immunol"},{"key":"pgen.1012328.ref014","doi-asserted-by":"crossref","first-page":"880568","DOI":"10.3389\/fpsyt.2022.880568","article-title":"Immune system abnormalities in schizophrenia: An integrative view and translational perspectives","volume":"13","author":"EA Ermakov","year":"2022","journal-title":"Front Psychiatry"},{"key":"pgen.1012328.ref015","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000356539","article-title":"The immunology of bipolar disorder","volume":"21","author":"IG Barbosa","year":"2014","journal-title":"Neuroimmunomodulation"},{"key":"pgen.1012328.ref016","doi-asserted-by":"crossref","first-page":"110581","DOI":"10.1016\/j.pnpbp.2022.110581","article-title":"Peripheral blood inflammatory markers in patients with attention deficit\/hyperactivity disorder (ADHD): A systematic review and meta-analysis","volume":"118","author":"B Misiak","year":"2022","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"issue":"7982","key":"pgen.1012328.ref017","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41586-023-06563-x","article-title":"Large-scale plasma proteomics comparisons through genetics and disease associations","volume":"622","author":"GH Eldjarn","year":"2023","journal-title":"Nature"},{"issue":"1","key":"pgen.1012328.ref018","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1038\/s41467-022-29650-5","article-title":"Genetic analysis of over half a million people characterises C-reactive protein loci","volume":"13","author":"S Said","year":"2022","journal-title":"Nat Commun"},{"issue":"1","key":"pgen.1012328.ref019","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1038\/s41467-021-21015-8","article-title":"GWAS for autoimmune Addison\u2019s disease identifies multiple risk loci and highlights AIRE in disease susceptibility","volume":"12","author":"D Eriksson","year":"2021","journal-title":"Nat Commun"},{"issue":"1","key":"pgen.1012328.ref020","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bpsgos.2021.03.002","article-title":"Investigating pleiotropy between depression and autoimmune diseases using the UK Biobank","volume":"1","author":"KP Glanville","year":"2021","journal-title":"Biol Psychiatry Glob Open Sci"},{"issue":"2","key":"pgen.1012328.ref021","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1038\/ng.3760","article-title":"Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease","volume":"49","author":"KM de Lange","year":"2017","journal-title":"Nat Genet"},{"issue":"7863","key":"pgen.1012328.ref022","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/s41586-021-03552-w","article-title":"Interpreting type 1 diabetes risk with genetics and single-cell epigenomics","volume":"594","author":"J Chiou","year":"2021","journal-title":"Nature"},{"issue":"3","key":"pgen.1012328.ref023","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1136\/annrheumdis-2020-218481","article-title":"Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms","volume":"80","author":"E L\u00f3pez-Isac","year":"2021","journal-title":"Ann Rheum Dis"},{"issue":"5","key":"pgen.1012328.ref024","article-title":"Identification of genetic risk loci and prioritization of genes and pathways for myasthenia gravis: A genome-wide association study","volume":"119","author":"International Myasthenia Gravis Genomics Consortium","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pgen.1012328.ref025","first-page":"100069","article-title":"Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine mapping in the MHC and genome wide","volume":"3","author":"PE Stuart","year":"2022","journal-title":"HGG Adv"},{"issue":"9","key":"pgen.1012328.ref026","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1002\/art.42154","article-title":"Comparative genetic analysis of psoriatic arthritis and psoriasis for the discovery of genetic risk factors and risk prediction modeling","volume":"74","author":"M Soomro","year":"2022","journal-title":"Arthritis Rheumatol"},{"issue":"7488","key":"pgen.1012328.ref027","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1038\/nature12873","article-title":"Genetics of rheumatoid arthritis contributes to biology and drug discovery","volume":"506","author":"the RACI consortium, the GARNET consortium","year":"2014","journal-title":"Nature"},{"issue":"12","key":"pgen.1012328.ref028","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/ng.3434","article-title":"Genetic association analyses implicate aberrant regulation of innate and adaptive immunity genes in the pathogenesis of systemic lupus erythematosus","volume":"47","author":"J Bentham","year":"2015","journal-title":"Nat Genet"},{"issue":"12","key":"pgen.1012328.ref029","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1038\/s41593-018-0275-1","article-title":"Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders","volume":"21","author":"RK Walters","year":"2018","journal-title":"Nat Neurosci"},{"issue":"8","key":"pgen.1012328.ref030","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1038\/s41588-019-0439-2","article-title":"Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa","volume":"51","author":"HJ Watson","year":"2019","journal-title":"Nat Genet"},{"issue":"12","key":"pgen.1012328.ref031","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1038\/s41380-019-0559-1","article-title":"A major role for common genetic variation in anxiety disorders","volume":"25","author":"KL Purves","year":"2020","journal-title":"Mol Psychiatry"},{"key":"pgen.1012328.ref032","article-title":"Genome-wide analyses of ADHD identify 27 risk loci, refine the genetic architecture and implicate several cognitive domains","author":"D Demontis","year":"2023","journal-title":"Nat Genet"},{"key":"pgen.1012328.ref033","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13229-017-0137-9","article-title":"Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia","volume":"8","author":"The Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium","year":"2017","journal-title":"Mol Autism"},{"issue":"8056","key":"pgen.1012328.ref034","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1038\/s41586-024-08468-9","article-title":"Genomics yields biological and phenotypic insights into bipolar disorder","volume":"639","author":"KS O\u2019Connell","year":"2025","journal-title":"Nature"},{"issue":"12","key":"pgen.1012328.ref035","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1016\/S2215-0366(20)30339-4","article-title":"A large-scale genome-wide association study meta-analysis of cannabis use disorder","volume":"7","author":"EC Johnson","year":"2020","journal-title":"Lancet Psychiatry"},{"issue":"3","key":"pgen.1012328.ref036","article-title":"Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies","volume":"188","author":"Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Electronic address: andrew.mcintosh@ed.ac.uk, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium","year":"2025","journal-title":"Cell"},{"issue":"5","key":"pgen.1012328.ref037","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/mp.2017.154","article-title":"Revealing the complex genetic architecture of obsessive\u2013compulsive disorder using meta-analysis","volume":"23","author":"International Obsessive Compulsive Disorder Foundation Genetics Collaborative (IOCDF-GC), OCD Collaborative Genetics Association Studies (OCGAS)","year":"2018","journal-title":"Mol Psychiatry"},{"issue":"8","key":"pgen.1012328.ref038","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1038\/s41380-020-0677-9","article-title":"Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium","volume":"25","author":"R Polimanti","year":"2020","journal-title":"Mol Psychiatry"},{"key":"pgen.1012328.ref039","article-title":"Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder","author":"CM Nievergelt","year":"2024","journal-title":"Nat Genet"},{"issue":"7906","key":"pgen.1012328.ref040","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1038\/s41586-022-04434-5","article-title":"Mapping genomic loci implicates genes and synaptic biology in schizophrenia","volume":"604","author":"V Trubetskoy","year":"2022","journal-title":"Nature"},{"issue":"3","key":"pgen.1012328.ref041","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1176\/appi.ajp.2018.18070857","article-title":"Interrogating the genetic determinants of Tourette\u2019s syndrome and other tic disorders through genome-wide association studies","volume":"176","author":"D Yu","year":"2019","journal-title":"Am J Psychiatry"},{"issue":"8","key":"pgen.1012328.ref042","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1001\/jamapsychiatry.2023.1808","article-title":"Transcriptome-wide structural equation modeling of 13 major psychiatric disorders for cross-disorder risk and drug repurposing","volume":"80","author":"AD Grotzinger","year":"2023","journal-title":"JAMA Psychiatry"},{"key":"pgen.1012328.ref043","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fcell.2019.00091","article-title":"TNFR1 and TNFR2 in the control of the life and death balance of macrophages","volume":"7","author":"H Wajant","year":"2019","journal-title":"Front Cell Dev Biol"},{"issue":"3","key":"pgen.1012328.ref044","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1002\/art.37819","article-title":"Tumor necrosis factor \u03b1\u2013 and interleukin\u20101\u03b2\u2013dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1","volume":"65","author":"J Wang","year":"2013","journal-title":"Arthritis Rheum"},{"key":"pgen.1012328.ref045","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.bbi.2018.02.013","article-title":"Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters","volume":"70","author":"M Del Giudice","year":"2018","journal-title":"Brain Behav Immun"},{"issue":"6","key":"pgen.1012328.ref046","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/s41380-018-0096-3","article-title":"What does plasma CRP tell us about peripheral and central inflammation in depression?","volume":"25","author":"JC Felger","year":"2020","journal-title":"Mol Psychiatry"},{"issue":"4","key":"pgen.1012328.ref047","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1159\/000097202","article-title":"Passage of cytokines across the blood-brain barrier","volume":"2","author":"WA Banks","year":"1995","journal-title":"Neuroimmunomodulation"},{"issue":"4","key":"pgen.1012328.ref048","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1093\/ecco-jcc\/jjab191","article-title":"Depression and inflammatory bowel disease: A bidirectional two-sample Mendelian randomization study","volume":"16","author":"J Luo","year":"2022","journal-title":"J Crohns Colitis"},{"issue":"11","key":"pgen.1012328.ref049","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/s41575-022-00634-6","article-title":"Depression and anxiety in inflammatory bowel disease: Epidemiology, mechanisms and treatment","volume":"19","author":"TH Bisgaard","year":"2022","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"pgen.1012328.ref050","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: When the immune system subjugates the brain","volume":"9","author":"R Dantzer","year":"2008","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"pgen.1012328.ref051","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.yfrne.2012.09.003","article-title":"Cytokine effects on the basal ganglia and dopamine function: The subcortical source of inflammatory malaise","volume":"33","author":"JC Felger","year":"2012","journal-title":"Front Neuroendocrinol"},{"key":"pgen.1012328.ref052","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1359-6101(02)00020-5","article-title":"The balance between IL-1 and IL-1Ra in disease","volume":"13","author":"WP Arend","year":"2002","journal-title":"Cytokine Growth Factor Rev"},{"key":"pgen.1012328.ref053","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbi.2016.03.010","article-title":"The blood-brain barrier in systemic inflammation","volume":"60","author":"A Varatharaj","year":"2017","journal-title":"Brain Behav Immun"},{"issue":"7087","key":"pgen.1012328.ref054","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/nature04671","article-title":"Synaptic scaling mediated by glial TNF-alpha","volume":"440","author":"D Stellwagen","year":"2006","journal-title":"Nature"},{"issue":"3","key":"pgen.1012328.ref055","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.neuron.2016.03.030","article-title":"Microglial TNF-\u03b1 suppresses cocaine-induced plasticity and behavioral sensitization","volume":"90","author":"GM Lewitus","year":"2016","journal-title":"Neuron"},{"issue":"1","key":"pgen.1012328.ref056","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s41398-024-02921-z","article-title":"Inflammatory mediators in major depression and bipolar disorder","volume":"14","author":"S Poletti","year":"2024","journal-title":"Transl Psychiatry"},{"key":"pgen.1012328.ref057","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.bbi.2021.07.009","article-title":"Associations of immunological proteins\/traits with schizophrenia, major depression and bipolar disorder: A bi-directional two-sample mendelian randomization study","volume":"97","author":"BI Perry","year":"2021","journal-title":"Brain Behav Immun"},{"issue":"3","key":"pgen.1012328.ref058","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1038\/s41588-022-01017-y","article-title":"An integrated framework for local genetic correlation analysis","volume":"54","author":"J Werme","year":"2022","journal-title":"Nat Genet"},{"issue":"11","key":"pgen.1012328.ref059","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1001\/jamapsychiatry.2024.2185","article-title":"Inflammatory biomarkers and risk of psychiatric disorders","volume":"81","author":"Y Zeng","year":"2024","journal-title":"JAMA Psychiatry"},{"issue":"2","key":"pgen.1012328.ref060","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bbi.2010.10.008","article-title":"Immune suppression and immune activation in depression","volume":"25","author":"J Blume","year":"2011","journal-title":"Brain Behav Immun"},{"issue":"7","key":"pgen.1012328.ref061","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1586\/14737175.7.7.789","article-title":"Inflammation and schizophrenia","volume":"7","author":"X Fan","year":"2007","journal-title":"Expert Rev Neurother"},{"key":"pgen.1012328.ref062","doi-asserted-by":"crossref","first-page":"106368","DOI":"10.1016\/j.psyneuen.2023.106368","article-title":"Cross-trait genome-wide association analysis of C-reactive protein level and psychiatric disorders","volume":"157","author":"G Hindley","year":"2023","journal-title":"Psychoneuroendocrinology"},{"issue":"4","key":"pgen.1012328.ref063","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1080\/15622975.2021.1961502","article-title":"C-reactive protein as a potential biomarker in psychiatric practice: Are we there yet?","volume":"23","author":"E Baysak","year":"2021","journal-title":"World J Biol Psychiatry"},{"issue":"10","key":"pgen.1012328.ref064","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1001\/jamapsychiatry.2014.1332","article-title":"Association of serum interleukin 6 and C-reactive protein in childhood with depression and psychosis in young adult life: A population-based longitudinal study","volume":"71","author":"GM Khandaker","year":"2014","journal-title":"JAMA Psychiatry"},{"issue":"4","key":"pgen.1012328.ref065","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/s41588-018-0081-4","article-title":"Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types","volume":"50","author":"HK Finucane","year":"2018","journal-title":"Nat Genet"},{"issue":"3","key":"pgen.1012328.ref066","article-title":"Immune-targeted therapies for depression: Current evidence for antidepressant effects of monoclonal antibodies","volume":"85","author":"MM Rizk","year":"2024","journal-title":"J Clin Psychiatry"},{"issue":"5","key":"pgen.1012328.ref067","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1111\/iji.12332","article-title":"What has GWAS done for HLA and disease associations?","volume":"44","author":"AE Kennedy","year":"2017","journal-title":"Int J Immunogenet"},{"issue":"1","key":"pgen.1012328.ref068","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1038\/s41439-022-00226-5","article-title":"Human leukocyte antigen super-locus: Nexus of genomic supergenes, SNPs, indels, transcripts, and haplotypes","volume":"9","author":"JK Kulski","year":"2022","journal-title":"Hum Genome Var"},{"issue":"2","key":"pgen.1012328.ref069","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/iid3.416","article-title":"Current research status of HLA in immune-related diseases","volume":"9","author":"B Liu","year":"2021","journal-title":"Immun Inflamm Dis"},{"key":"pgen.1012328.ref070","author":"FinnGen","year":"2024"},{"issue":"1","key":"pgen.1012328.ref071","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s40246-018-0185-z","article-title":"The X chromosome and sex-specific effects in infectious disease susceptibility","volume":"13","author":"H Schurz","year":"2019","journal-title":"Hum Genom"},{"issue":"9","key":"pgen.1012328.ref072","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/nri2394","article-title":"The X-files in immunity: Sex-based differences predispose immune responses","volume":"8","author":"EN Fish","year":"2008","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"pgen.1012328.ref073","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0113684","article-title":"Accounting for eXentricities: analysis of the X chromosome in GWAS reveals X-linked genes implicated in autoimmune diseases","volume":"9","author":"D Chang","year":"2014","journal-title":"PLoS One"},{"key":"pgen.1012328.ref074","doi-asserted-by":"crossref","first-page":"106214","DOI":"10.1016\/j.nbd.2023.106214","article-title":"Sex representation in neurodegenerative and psychiatric disorders\u2019 preclinical and clinical studies","volume":"184","author":"M DuMont","year":"2023","journal-title":"Neurobiol Dis"},{"key":"pgen.1012328.ref075","article-title":"The inactive X chromosome as a female protector in autism and beyond","author":"M Talukdar","year":"2026","journal-title":"Nat Genet"},{"issue":"4","key":"pgen.1012328.ref076","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/s41588-020-0594-5","article-title":"Minimal phenotyping yields genome-wide association signals of low specificity for major depression","volume":"52","author":"N Cai","year":"2020","journal-title":"Nat Genet"},{"issue":"7","key":"pgen.1012328.ref077","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1038\/s41562-023-01579-9","article-title":"Participation bias in the UK Biobank distorts genetic associations and downstream analyses","volume":"7","author":"T Schoeler","year":"2023","journal-title":"Nat Hum Behav"},{"issue":"2","key":"pgen.1012328.ref078","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1007\/s12035-019-01737-z","article-title":"The role of aberrations in the immune-inflammatory response system (IRS) and the compensatory immune-regulatory reflex system (CIRS) in different phenotypes of schizophrenia: The IRS-CIRS theory of schizophrenia","volume":"57","author":"C Roomruangwong","year":"2020","journal-title":"Mol Neurobiol"},{"issue":"1","key":"pgen.1012328.ref079","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/nyas.13712","article-title":"Inflammation in psychiatric disorders: What comes first?","volume":"1437","author":"ME Bauer","year":"2019","journal-title":"Ann N Y Acad Sci"},{"issue":"11","key":"pgen.1012328.ref080","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ng.3406","article-title":"An atlas of genetic correlations across human diseases and traits","volume":"47","author":"B Bulik-Sullivan","year":"2015","journal-title":"Nat Genet"},{"issue":"1","key":"pgen.1012328.ref081","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.biopsych.2022.05.029","article-title":"Pervasive downward bias in estimates of liability-scale heritability in genome-wide association study meta-analysis: A simple solution","volume":"93","author":"AD Grotzinger","year":"2023","journal-title":"Biol Psychiatry"},{"issue":"5","key":"pgen.1012328.ref082","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/s41562-019-0566-x","article-title":"Genomic structural equation modelling provides insights into the multivariate genetic architecture of complex traits","volume":"3","author":"AD Grotzinger","year":"2019","journal-title":"Nat Hum Behav"},{"key":"pgen.1012328.ref083","author":"JM Lawrence","year":"2024"},{"issue":"6","key":"pgen.1012328.ref084","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1002\/jclp.23091","article-title":"Construction and validation of a self-direction measure for mental health care","volume":"77","author":"A de Vries","year":"2021","journal-title":"J Clin Psychol"},{"key":"pgen.1012328.ref085","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.bbi.2018.02.013","article-title":"Rethinking IL-6 and CRP: Why they are more than inflammatory biomarkers, and why it matters","volume":"70","author":"M Del Giudice","year":"2018","journal-title":"Brain Behav Immun"},{"issue":"1","key":"pgen.1012328.ref086","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s42003-025-07453-w","article-title":"The genomic architecture of circulating cytokine levels points to drug targets for immune-related diseases","volume":"8","author":"MJ Konieczny","year":"2025","journal-title":"Commun Biol"},{"issue":"1","key":"pgen.1012328.ref087","doi-asserted-by":"crossref","first-page":"6939","DOI":"10.1038\/s41467-022-34688-6","article-title":"Pleiotropic genetic architecture and novel loci for C-reactive protein levels","volume":"13","author":"F Koskeridis","year":"2022","journal-title":"Nat Commun"},{"key":"pgen.1012328.ref088","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"G Hemani","year":"2018","journal-title":"eLife"}],"updated-by":[{"DOI":"10.1371\/journal.pgen.1012328","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000}}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012328","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:57:02Z","timestamp":1791309422000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1012328"}},"subtitle":[],"editor":[{"given":"Timothy","family":"Shaw","sequence":"first","affiliation":[{"name":"Moffitt Cancer Center","place":["UNITED STATES OF AMERICA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,30]]},"references-count":88,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,30]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1012328","relation":{},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,30]]}}}