Abstract

Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (PAgP-Ger < 0.05; PCAD < 5 × 10−8; concordant effect direction) and were replicated in an independent GWAS meta-analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed significant association (PD[Replication]: P = 0.008 OR = 1.09, 95% CI = [1.02–1.16]; PD [Discovery + Replication]: P = 0.0002, OR = 1.11, 95% CI = [1.05–1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8 expression were reported. Our data adds to the shared genetic basis of CAD and PD and indicate that the observed association of the two disease conditions cannot be solely explained by shared environmental risk factors. We conclude that the molecular pathway shared by CAD and PD involves VAMP8 function, which has a role in membrane vesicular trafficking, and is manipulated by pathogens to corrupt host immune defense.

Details

Title
Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus
Author
Munz, Matthias 1   VIAFID ORCID Logo  ; Richter, Gesa M 2 ; Loos, Bruno G 3 ; Jepsen, Søren 4 ; Divaris, Kimon 5   VIAFID ORCID Logo  ; Offenbacher, Steven 6 ; Teumer, Alexander 7   VIAFID ORCID Logo  ; Holtfreter, Birte 8   VIAFID ORCID Logo  ; Kocher, Thomas 8 ; Bruckmann, Corinna 9 ; Jockel-Schneider, Yvonne 10 ; Graetz, Christian 11 ; Munoz, Loreto 12 ; Bhandari, Anita 12 ; Tennstedt, Stephanie 12 ; Staufenbiel, Ingmar 13 ; van der Velde, Nathalie 14 ; Uitterlinden, André G 15 ; Lisette C P G M de Groot 16   VIAFID ORCID Logo  ; Wellmann, Jürgen 17 ; Berger, Klaus 17 ; Krone, Bastian 18 ; Hoffmann, Per 19   VIAFID ORCID Logo  ; Laudes, Matthias 20 ; Lieb, Wolfgang 21 ; Franke, Andre 21   VIAFID ORCID Logo  ; Dommisch, Henrik 2 ; Erdmann, Jeanette 12   VIAFID ORCID Logo  ; Schaefer, Arne S 2   VIAFID ORCID Logo 

 Charité – University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, Berlin, Germany; Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany 
 Charité – University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, Berlin, Germany 
 Department of Periodontology and Oral Biochemistry, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands 
 Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany 
 Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, USA 
 Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, USA 
 Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany 
 Unit of Periodontology, Department of Restorative Dentistry, Periodontology, Endodontology, Preventive Dentistry and Pedodontics, Dental School, University Medicine Greifswald, Greifswald, Germany 
 Department of Conservative Dentistry and Periodontology, Medical University Vienna, School of Dentistry, Vienna, Austria 
10  Department of Periodontology, Clinic of Preventive Dentistry and Periodontology, University Medical Center of the Julius-Maximilians-University, Würzburg, Germany 
11  Department of Conservative Dentistry, Unit of Periodontology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany 
12  Institute for Cardiogenetics, University of Lübeck, Lübeck, Germany; DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany; University Heart Center Luebeck, Lübeck, Germany 
13  Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Hannover, Germany 
14  Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Internal Medicine section of Geriatrics, Amsterdam Medical Center, Amsterdam, The Netherlands 
15  Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands 
16  Wageningen University, Division of Human Nutrition, Wageningen, The Netherlands 
17  Institute of Epidemiology and Social Medicine, University Münster, Münster, Germany 
18  Institute of Medical Informatics, Biometry and Epidemiology, University Clinic Essen, Essen, Germany 
19  Institute of Human Genetics, University of Bonn, Bonn, Germany; Human Genomics Research Group, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland 
20  Department of Medicine 1, University of Kiel, Kiel, Germany 
21  Institute of Epidemiology, Christian-Albrechts-University, Kiel, Germany 
Pages
1-10
Publication year
2018
Publication date
Sep 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2102898518
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.