{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T09:37:24Z","timestamp":1793353044790,"version":"4.5.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["495133518"],"award-info":[{"award-number":["495133518"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["542489987"],"award-info":[{"award-number":["542489987"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Community Medicine Research net of the University of Greifswald"},{"DOI":"10.13039\/501100002347","name":"Social Ministry of the Federal State of Mecklenburg-West Pomerania BMBF","doi-asserted-by":"publisher","award":["03ZIK012"],"award-info":[{"award-number":["03ZIK012"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Siemens Healthineers, Erlangen, Germany and the Federal State of Mecklenburg-West Pomerania"},{"name":"The Dortmund Health Study"},{"name":"German Migraine & Headache Society"},{"name":"Institute of Epidemiology and Social Medicine University of Muenster and genotyping supported by the BMBF","award":["01ER0816"],"award-info":[{"award-number":["01ER0816"]}]},{"name":"Institute of Epidemiology and Social Medicine University of Muenster and genotyping supported by the BMBF","award":["01ER1506"],"award-info":[{"award-number":["01ER1506"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Periodontitis is a complex inflammatory disease in which chronic immune activation drives destruction of periodontal soft tissues and alveolar bone. Although early-onset forms show high heritability, much genetic risk remains unresolved. To identify shared genetic signals across early- and later-onset periodontitis, we combined two European genome-wide association study datasets (3183 cases, 10\u2009326 controls) and applied Fisher\u2019s combined probability test (FCOMB) and effect-size-based genome-wide association meta-analysis (GWAMA) across &amp;gt;\u20097 million variants to capture shared signals with either heterogeneous or more concordant effect sizes. We confirmed known associations at SIGLEC5 and DEFA1A3 and identified several additional suggestive loci. Among these, FCOMB highlighted the strongest signal at the long non-coding RNA LINC01541 (rs11876034, P\u00a0=\u20091.7\u2009\u00d7\u200910\u22126). We evaluated the biological relevance of LINC01541 by repressing it in gingival fibroblasts using CRISPR interference. Knockdown led to significant downregulation of inflammatory mediators, including CSF2 and CSF3, regulators of neutrophil recruitment, members of the interleukin (IL) family (IL1B, IL36B, IL36RN), and chemokines (CXCL5, CXCL8, CCL20). Six of the top ten differentially expressed genes belonged to an epithelial keratinization expression cluster. Gene-set enrichment analyses following linc01541 knockdown demonstrated repression of cytokine signaling, with IL-10 signaling most affected (padj\u00a0=\u20095.3\u2009\u00d7\u200910\u221214; AUC\u2009=\u20090.81), alongside activation of cell-cycle pathways (padj\u00a0=\u20093.3\u2009\u00d7\u200910\u221224; AUC\u2009=\u20090.73). We demonstrated the utility of aggregating heterogeneous samples to detect modest but biologically meaningful genetic effects. The convergence of the genetic association at LINC01541 with functional evidence suggests that this lncRNA modulates an upstream mucosal inflammatory axis relevant to periodontal pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddag039","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T11:20:08Z","timestamp":1778498408000},"source":"Crossref","is-referenced-by-count":2,"title":["Combined periodontitis GWAS identifies\n                    <i>LINC01541<\/i>\n                    as a regulator of innate immunity in the oral mucosa"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4825-4670","authenticated-orcid":false,"given":"Gesa M","family":"Richter","sequence":"first","affiliation":[{"name":"Department of Periodontology, Oral Medicine and Oral Surgery, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , A\u00dfmannshauser Str. 4-6, 14197 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3251-514X","authenticated-orcid":false,"given":"Oluwabukunmi M","family":"Akinloye","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics and Statistics, Christian-Albrechts-University Kiel , Brunswiker Str. 10, 24105 Kiel ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"K\u00fchnlenz","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Oral Medicine and Oral Surgery, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , A\u00dfmannshauser Str. 4-6, 14197 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"January 3rd","family":"Weiner","sequence":"additional","affiliation":[{"name":"Core Unit Bioinformatics, Berlin Institute of Health at Charit\u00e9 Berlin , Chariteplatz 110117 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6541-3127","authenticated-orcid":false,"given":"Birte","family":"Holtfreter","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry, Periodontology and Endodontology, University Medicine Greifswald , Walther-Rathenau-Stra\u00dfe 42A, 17489 Greifswald ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7471-0254","authenticated-orcid":false,"given":"Alicia","family":"de Coo","sequence":"additional","affiliation":[{"name":"Genomics and Bioinformatics, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela , Av. Barcelona, 15782 Santiago de Compostela ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2813-8928","authenticated-orcid":false,"given":"Silvia","family":"Diz-De Almeida","sequence":"additional","affiliation":[{"name":"Genomics and Bioinformatics, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela , Av. Barcelona, 15782 Santiago de Compostela ,","place":["Spain"]},{"name":"Fundaci\u00f3n P\u00fablica Galega de Medicina Xen\u00f3mica, Sistema Galego de Sa\u00fade (SERGAS), Instituto de Investigaci\u00f3n Sanitaria de Santiago (IDIS), R\u00faa da Choupana s\/n, 15706 Santiago de Compostela ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8794-552X","authenticated-orcid":false,"given":"Bruno G","family":"Loos","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam , Gustav Mahlerlaan 3004, 1081 LA Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4160-5837","authenticated-orcid":false,"given":"S\u00f8ren","family":"Jepsen","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Operative and Preventive Dentistry, University of Bonn , Welschnonnenstra\u00dfe 17, 53111 Bonn ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-2651","authenticated-orcid":false,"given":"Henrik","family":"Dommisch","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Oral Medicine and Oral Surgery, Charit\u00e9 - Universit\u00e4tsmedizin Berlin , A\u00dfmannshauser Str. 4-6, 14197 Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3165-3624","authenticated-orcid":false,"given":"Corinna","family":"Bruckmann","sequence":"additional","affiliation":[{"name":"Division of Periodontology, University Clinic of Dentistry, Medical University of Vienna , Sensengasse 2a, 1090 Vienna ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6169-6812","authenticated-orcid":false,"given":"Ines","family":"Kapferer-Seebacher","sequence":"additional","affiliation":[{"name":"Department of Dental and Oral Medicine and Cranio-Maxillofacial and Oral Surgery, University Hospital for Conservative Dentistry and Periodontology, Medical University Innsbruck , Anichstra\u00dfe 35, A - 6020 Innsbruck ,","place":["Austria"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-0605","authenticated-orcid":false,"given":"Georg","family":"Homuth","sequence":"additional","affiliation":[{"name":"Department of Functional Genomics, Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald , Felix-Hausdorff-Str. 8, 17475 Greifswald 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