TY  - JOUR
A1  - Munz, Matthias
A1  - Richter, Gesa M.
A1  - Loos, Bruno G.
A1  - Jepsen, Søren
A1  - Divaris, Kimon
A1  - Offenbacher, Steven
A1  - Teumer, Alexander
A1  - Holtfreter, Birte
A1  - Kocher, Thomas
A1  - Bruckmann, Corinna
A1  - Jockel-Schneider, Yvonne
A1  - Graetz, Christian
A1  - Munoz, Loreto
A1  - Bhandari, Anita
A1  - Tennstedt, Stephanie
A1  - Staufenbiel, Ingmar
A1  - van der Velde, Nathalie
A1  - Uitterlinden, André G.
A1  - de Groot, Lisette C. P. G. M.
A1  - Wellmann, Jürgen
A1  - Berger, Klaus
A1  - Krone, Bastian
A1  - Hoffmann, Per
A1  - Laudes, Matthias
A1  - Lieb, Wolfgang
A1  - Andre, Franke
A1  - Dommisch, Henrik
A1  - Erdmann, Jeanette
A1  - Schaefer, Arne S.
T1  - Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus
JF  - Scientific Reports
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.
KW  - vesicle-associated membrane protein 8 (VAMP8)
KW  - ADAM metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS7)
KW  - shared genetic basis
KW  - genome-wide association studies (GWAS)
KW  - GWAS meta-analysis
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231647
VL  - 8
ER  -