{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:05:19Z","timestamp":1792785919016,"version":"4.5.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":273,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King\u2019s-China Scholarship Council","award":["202108060123"],"award-info":[{"award-number":["202108060123"]}],"id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"crossref"}]},{"name":"The King\u2019s-China Scholarship Council","id":[{"id":"https:\/\/ror.org\/04atp4p48","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Schizophrenia (SCZ) and systemic lupus erythematosus (SLE) exhibit epidemiological overlap, suggesting shared genetic underpinnings. Using the largest SLE genome-wide association study (GWAS) to date, we identified a significant genetic correlation between SCZ and SLE (rg\u2009=\u20090.25, p\u2009=\u20099.0\u2009\u00d7\u200910\u22124). Cross-trait analysis nominated multiple candidate shared loci outside the major histocompatibility complex (MHC), most with aligned effects. The strongest candidate shared association was found at the FURIN-FES locus, previously implicated in SCZ and newly associated with SLE. In addition to FURIN-FES, FCGR2A, DOT1L and an intergenic noncoding RNA locus on chromosome 2 showed additional evidence consistent with shared association. Functional annotation showed that this locus modulated the expression of FURIN, which encodes a proprotein convertase involved in diverse biological processes, and FES, which encodes a tyrosine kinase important in innate immune signalling. The shared risk allele was also associated with altered plasma levels of FURIN, FES, and their functional partners (GDF2, BMP10, NTF4, FER). Tissue- and cell-type-specific eQTL analysis revealed distinct regulatory effects: FURIN expression was perturbed in neuronal and immune cells, while FES expression was altered in immune cells. Mendelian randomisation supported a causal role for FES protein in both disorders. These findings highlight that pleiotropy at the FURIN-FES locus for SCZ and SLE is compatible with disease-specific mechanisms. This underscores that shared genetics across traits does not necessarily mean shared biology.<\/jats:p>","DOI":"10.1093\/hmg\/ddag099","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:21:22Z","timestamp":1789672882000},"source":"Crossref","is-referenced-by-count":0,"title":["Shared genetic architecture of schizophrenia and lupus identifies pleiotropic loci with distinct downstream mechanisms"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8481-6991","authenticated-orcid":false,"given":"Chen","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , St Thomas Street, London , SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1805-6278","authenticated-orcid":false,"given":"Nick","family":"Dand","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , St Thomas Street, London , SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy W","family":"Butler","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , St Thomas Street, London , SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariella","family":"Amar","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , St Thomas Street, London , SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, The First Affiliated Hospital of Anhui Medical University , Hefei, Anhui,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7392-2528","authenticated-orcid":false,"given":"Pinelopi Maria","family":"Triantafyllou","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , St Thomas Street, London , SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1754-8932","authenticated-orcid":false,"given":"David L","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , St Thomas Street, London , SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1123-1464","authenticated-orcid":false,"given":"Timothy J","family":"Vyse","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, King\u2019s College London , St Thomas Street, London , SE1 9RT,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"2026100119481630100_ref1","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2022.880568","article-title":"Immune system abnormalities in schizophrenia: an integrative view and translational perspectives. 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