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

Matthias Munz, Gesa M. Richter, Bruno G. Loos, Søren Jepsen, Kimon Divaris, Steven Offenbacher, Alexander Teumer, Birte Holtfreter, Thomas Kocher, Corinna Bruckmann, Yvonne Jockel-Schneider, Christian Graetz, Loreto Munoz, Anita Bhandari, Stephanie Tennstedt, Ingmar Staufenbiel, Nathalie Van Der Velde, André G. Uitterlinden, Lisette C.P.G.M. De Groot, Jürgen Wellmann & 9 others Klaus Berger, Bastian Krone, Per Hoffmann, Matthias Laudes, Wolfgang Lieb, Andre Franke, Henrik Dommisch, Jeanette Erdmann, Arne S. Schaefer

Research output: Contribution to journalArticleAcademicpeer-review

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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.
LanguageEnglish
Article number13678
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 12 Sep 2018

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Periodontitis
Genome-Wide Association Study
Meta-Analysis
Coronary Artery Disease
Single Nucleotide Polymorphism
Aggressive Periodontitis
Haplotypes
Patient Selection
Joints
Alleles
Membranes

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Munz, M., Richter, G. M., Loos, B. G., Jepsen, S., Divaris, K., Offenbacher, S., ... Schaefer, A. S. (2018). Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus. Scientific Reports, 8(1), [13678]. https://doi.org/10.1038/s41598-018-31980-8
Munz, Matthias ; Richter, Gesa M. ; Loos, Bruno G. ; Jepsen, Søren ; Divaris, Kimon ; Offenbacher, Steven ; Teumer, Alexander ; Holtfreter, Birte ; Kocher, Thomas ; Bruckmann, Corinna ; Jockel-Schneider, Yvonne ; Graetz, Christian ; Munoz, Loreto ; Bhandari, Anita ; Tennstedt, Stephanie ; Staufenbiel, Ingmar ; Van Der Velde, Nathalie ; Uitterlinden, André G. ; De Groot, Lisette C.P.G.M. ; Wellmann, Jürgen ; Berger, Klaus ; Krone, Bastian ; Hoffmann, Per ; Laudes, Matthias ; Lieb, Wolfgang ; Franke, Andre ; Dommisch, Henrik ; Erdmann, Jeanette ; Schaefer, Arne S. / Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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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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Munz, M, Richter, GM, Loos, BG, Jepsen, S, Divaris, K, Offenbacher, S, Teumer, A, Holtfreter, B, Kocher, T, Bruckmann, C, Jockel-Schneider, Y, Graetz, C, Munoz, L, Bhandari, A, Tennstedt, S, Staufenbiel, I, Van Der Velde, N, Uitterlinden, AG, De Groot, LCPGM, Wellmann, J, Berger, K, Krone, B, Hoffmann, P, Laudes, M, Lieb, W, Franke, A, Dommisch, H, Erdmann, J & Schaefer, AS 2018, 'Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus', Scientific Reports, vol. 8, no. 1, 13678. https://doi.org/10.1038/s41598-018-31980-8

Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus. / Munz, Matthias; Richter, Gesa M.; Loos, Bruno G.; Jepsen, Søren; Divaris, Kimon; Offenbacher, Steven; Teumer, Alexander; Holtfreter, Birte; Kocher, Thomas; Bruckmann, Corinna; Jockel-Schneider, Yvonne; Graetz, Christian; Munoz, Loreto; Bhandari, Anita; Tennstedt, Stephanie; Staufenbiel, Ingmar; Van Der Velde, Nathalie; Uitterlinden, André G.; De Groot, Lisette C.P.G.M.; Wellmann, Jürgen; Berger, Klaus; Krone, Bastian; Hoffmann, Per; Laudes, Matthias; Lieb, Wolfgang; Franke, Andre; Dommisch, Henrik; Erdmann, Jeanette; Schaefer, Arne S.

In: Scientific Reports, Vol. 8, No. 1, 13678, 12.09.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus

AU - Munz, Matthias

AU - Richter, Gesa M.

AU - Loos, Bruno G.

AU - Jepsen, Søren

AU - Divaris, Kimon

AU - Offenbacher, Steven

AU - Teumer, Alexander

AU - Holtfreter, Birte

AU - Kocher, Thomas

AU - Bruckmann, Corinna

AU - Jockel-Schneider, Yvonne

AU - Graetz, Christian

AU - Munoz, Loreto

AU - Bhandari, Anita

AU - Tennstedt, Stephanie

AU - Staufenbiel, Ingmar

AU - Van Der Velde, Nathalie

AU - Uitterlinden, André G.

AU - De Groot, Lisette C.P.G.M.

AU - Wellmann, Jürgen

AU - Berger, Klaus

AU - Krone, Bastian

AU - Hoffmann, Per

AU - Laudes, Matthias

AU - Lieb, Wolfgang

AU - Franke, Andre

AU - Dommisch, Henrik

AU - Erdmann, Jeanette

AU - Schaefer, Arne S.

PY - 2018/9/12

Y1 - 2018/9/12

N2 - 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.

AB - 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.

U2 - 10.1038/s41598-018-31980-8

DO - 10.1038/s41598-018-31980-8

M3 - Article

VL - 8

JO - Scientific Reports

T2 - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

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ER -