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Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.

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, 23562, Lübeck, 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. Department of Periodontology, Clinic of Preventive Dentistry and Periodontology, University Medical Center of the Julius-Maximilians-University, Würzburg, Germany. Department of Conservative Dentistry, Unit of Periodontology, University Medical Center Schleswig-Holstein, Campus Kiel, Germany. DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, 23562, Germany. University Heart Center Luebeck, 23562, Lübeck, Germany. Department of Conservative Dentistry, Periodontology and Preventive Dentistry, Hannover Medical School, Hannover, Germany. Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands. Department of Internal Medicine section of Geriatrics, Amsterdam Medical Center, Amsterdam, The Netherlands. Wageningen University, Division of Human Nutrition, Wageningen, The Netherlands. Institute of Epidemiology and Social Medicine, University Münster, Münster, Germany. Institute of Medical Informatics, Biometry and Epidemiology, University Clinic Essen, Essen, Germany. Institute of Human Genetics, University of Bonn, Bonn, Germany. Human Genomics Research Group, Department of Biomedicine, University Hospital of Basel, Basel, Switzerland. Department of Medicine 1, University of Kiel, Kiel, Germany. Institute of Epidemiology, Christian-Albrechts-University, Kiel, 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. arne.schaefer@charite.de.

Scientific reports. 2018;(1):13678
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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.

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Publication Type : Meta-Analysis

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