{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:23:47Z","timestamp":1780619027565,"version":"3.54.1"},"reference-count":32,"publisher":"SAGE Publications","issue":"8","license":[{"start":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T00:00:00Z","timestamp":1493769600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"The Federal Ministry of Education and Research","award":["01GR0468"],"award-info":[{"award-number":["01GR0468"]}]},{"name":"US-American National Institute of Health","award":["RO1-DE022527, UL1-TR001111, and RO1-DE021418"],"award-info":[{"award-number":["RO1-DE022527, UL1-TR001111, and RO1-DE021418"]}]},{"name":"The Institute of Epidemiology and Social Medicine University of Muenster funded Blood collection in the Dortmund Health Study and the Federal Ministry of Research and Education","award":["01ER0816"],"award-info":[{"award-number":["01ER0816"]}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","award":["429\/09"],"award-info":[{"award-number":["429\/09"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Research Foundation DFG (Deutsche Forschungsgemeinschaft","award":["GZ: SCHA 1582\/3-1 and SCHA 1582\/4-1"],"award-info":[{"award-number":["GZ: SCHA 1582\/3-1 and SCHA 1582\/4-1"]}]},{"name":"Federal Ministry of Education and Research BMBF","award":["FKZ 0315540A"],"award-info":[{"award-number":["FKZ 0315540A"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:p>\n                    Periodontitis is a common dysbiotic inflammatory disease with an estimated heritability of 50%. Due to the limited sample size of available periodontitis cohorts and the underlying trait heterogeneity, genome-wide association studies (GWAS) of chronic periodontitis (CP) have been unsuccessful in discovering susceptibility factors. A strategy that combines agnostic GWAS with a well-powered candidate-gene approach has the potential to discover novel loci. We combined RNA-seq data from gingival tissues with quantitative trait loci (QTLs) that were identified in a F\n                    <jats:sub>2<\/jats:sub>\n                    -cross of mice resistant and susceptible to infection with oral bacterial pathogens. Four genes, which were located within the mapped QTLs, showed differential expression. The chromosomal regions across the human orthologous were interrogated for putative periodontitis-associated variants using existing GWAS data from a German case-control sample of aggressive periodontitis (AgP; 651 cases, 4,001 controls), the most severe and early onset form of periodontitis. Two haplotype blocks, one upstream to the coding region of UGT2A1 (rs146712414, P = 9.1 \u00d7 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    ; odds ratio [OR], 1.34; 95% confidence interval [CI], 1.16\u20131.56) and one downstream of the genes PF4\/PPBP\/CXCL5 (rs1595009, P = 1.3 \u00d7 10\n                    <jats:sup>\u22124<\/jats:sup>\n                    ; OR, 1.32; 95% CI, 1.15\u20131.52), were associated with AgP. The association of rs1595009 was validated in an independent cohort of CP of European Americans (1,961 cases and 1,864 controls; P = 0.03; OR, 1.45; 95% CI, 1.01\u20131.29). This association was further replicated in another sample of 399 German CP cases (disease onset &lt;60 y of age) and 1,633 controls ( P = 0.03; OR, 1.75; 95% CI, 1.06\u20132.90). The combined estimates of association from all samples were P = 2.9 \u00d7 10\n                    <jats:sup>\u22125<\/jats:sup>\n                    (OR, 1.2; 95% CI, 1.1\u20131.3). This study shows the strength of combining QTL mapping and RNA-Seq data from a mouse model with association studies in human case-control samples to identify genetic risk variants of periodontitis.\n                  <\/jats:p>","DOI":"10.1177\/0022034517706311","type":"journal-article","created":{"date-parts":[[2017,5,3]],"date-time":"2017-05-03T14:38:56Z","timestamp":1493822336000},"page":"945-952","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["The\n                    <i>PF4\/PPBP\/CXCL5<\/i>\n                    Gene Cluster Is Associated with Periodontitis"],"prefix":"10.1177","volume":"96","author":[{"given":"A.","family":"Shusterman","sequence":"first","affiliation":[{"name":"Department of Prosthodontics, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Munz","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Synoptic Medicine, Institute for Dental and Craniofacial Sciences, Charit\u00e9\u2013University Medicine Berlin, Berlin, Germany"},{"name":"Institute for Integrative and Experimental Genomics, University Medical Center Schleswig-Holstein\u2013Campus L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Richter","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Synoptic Medicine, Institute for Dental and Craniofacial Sciences, Charit\u00e9\u2013University Medicine Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Jepsen","sequence":"additional","affiliation":[{"name":"Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Lieb","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology, Biobank popgen, Christian-Albrechts-University, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Krone","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Biometry and Epidemiology, University Clinic Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of Bonn, Bonn, Germany"},{"name":"Germany und Human Genomics Research Group, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Laudes","sequence":"additional","affiliation":[{"name":"Clinic of Internal Medicine, University Clinic Schleswig-Holstein, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Wellmann","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Social Medicine, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Berger","sequence":"additional","affiliation":[{"name":"Institute of Epidemiology and Social Medicine, University of M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kocher","sequence":"additional","affiliation":[{"name":"Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pedodontics, Dental School, University Medicine Greifswald, Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Offenbacher","sequence":"additional","affiliation":[{"name":"University of North Carolina\u2013Chapel Hill, School of Dentistry, Department of Periodontology, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Divaris","sequence":"additional","affiliation":[{"name":"University of North Carolina\u2013Chapel Hill, School of Dentistry, Department of Pediatric Dentistry, Chapel Hill, NC, USA"},{"name":"University of North Carolina\u2013Chapel Hill, Gillings School of Global Public Health, Department of Epidemiology, Chapel Hill, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Franke","sequence":"additional","affiliation":[{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Clinic of Internal Medicine, University Clinic Schleswig-Holstein, Kiel, Germany"},{"name":"Institute of Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Dommisch","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Synoptic Medicine, Institute for Dental and Craniofacial Sciences, Charit\u00e9\u2013University Medicine Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Maurice and Gabriella Goldschleger School of Dental Medicine, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.S.","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Department of Periodontology and Synoptic Medicine, Institute for Dental and Craniofacial Sciences, Charit\u00e9\u2013University Medicine Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Houri-Haddad","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, Hadassah Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.A.","family":"Iraqi","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2017,5,3]]},"reference":[{"key":"bibr1-0022034517706311","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a115184"},{"key":"bibr2-0022034517706311","doi-asserted-by":"publisher","DOI":"10.1007\/s00103-012-1492-5"},{"key":"bibr3-0022034517706311","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt299"},{"key":"bibr4-0022034517706311","doi-asserted-by":"publisher","DOI":"10.1902\/jop.1993.64.12.1205"},{"key":"bibr5-0022034517706311","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12253"},{"key":"bibr6-0022034517706311","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512447951"},{"key":"bibr7-0022034517706311","doi-asserted-by":"crossref","unstructured":"Divaris K, Monda KL, North KE, Olshan AF, Reynolds LM, Hsueh WC, Lange EM, Moss K, Barros SP, Weyant RJ, et al. 2013. 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