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

TitelGenome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.
MedientypJournal Article
Jahr der Veröffentlichung2018
AutorenMunz 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, Schäefer AS
JournalSci Rep
Volume8
Ausgabe1
Pagination13678
Datum der Veröffentlichung2018 Sep 12
ISSN2045-2322
Zusammenfassung

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 (P < 0.05; P < 5 × 10; 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.

DOI10.1038/s41598-018-31980-8
Alternate JournalSci Rep
PubMed ID30209331
Grant ListSCHA 1582/3-1 / / Deutsche Forschungsgemeinschaft (German Research Foundation) /