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
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 13678
ER -