Genomweite Assoziationsstudie zur Identifikation Genetischer Risikofaktoren der Parodontitis
Zusammenfassung der Projektergebnisse
This research project conducted a GWAS and meta-analyses of PD and CAD to identify novel genetic risk variants. Four novel risk loci with genome-wide significance (P < 5 10E-08) were identified (DEFA1A3, SIGLEC5, LOC107964137, MTND1P5), and the associations of two additional loci were validated (VAMP8, PLG). In addition, the shared genetic basis of PD and CAD was confirmed and expanded. This study did not give evidence for a shared genetic basis of RA and T2D with PD. Furthermore, genotyping of 600 AgP cases and 6.940 German controls with the Illumina HumanExome chip 12v1 could not identify nonsynonymous PD risk alleles with large effect sizes. The identification and characterization of putative causative variants of PD is ongoing. CNV analyses for the copy number variable locus DEF1A3 suggested a single overrepresented haplotype that might increase PD risk. In current works, we are matching our SNP and CNV data and aim phasing the SNP and CNV haplotypes computationally. Additionally, we performed a G x S interaction study and give evidence that genetic variants at the genes SOST, SSH1, ST8SIA1, and BMP7 increase the disease susceptibility for AgP by interaction with cigarette smoke.
Projektbezogene Publikationen (Auswahl)
- Genome-wide association study of biologically informed periodontal complex traits offers novel insights into the genetic basis of periodontal disease. Hum Mol Genet. 2016 May 15;25(10):2113-2129
Offenbacher S, Divaris K, Barros SP, Moss KL, Marchesan JT, Morelli T, Zhang S, Kim S, Sun L, Beck JD, Laudes M, Munz M, Schaefer AS, North KE
(Siehe online unter https://doi.org/10.1093/hmg/ddw069) - A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis. Hum Mol Genet. 2017 Jul 1;26(13):2577-2588
Munz M, Willenborg C, Richter GM, Jockel-Schneider Y, Graetz C, Staufenbiel I, Wellmann J, Berger K, Krone B, Hoffmann P, van der Velde N, Uitterlinden AG, de Groot LCPGM, Sawalha AH, Direskeneli H, Saruhan-Direskeneli G, Guzeldemir-Akcakanat E, Keceli HG, Laudes M, Noack B, Teumer A, Holtfreter B, Kocher T, Eickholz P, Meyle J, Doerfer C, Bruckmann C, Lieb W, Franke A, Schreiber S, Nohutcu RM, Erdmann J, Loos BG, Jepsen S, Dommisch H, Schaefer AS
(Siehe online unter https://doi.org/10.1093/hmg/ddx151) - A haplotype block downstream of plasminogen is associated with chronic and aggressive periodontitis. J Clin Periodontol. 2017 Oct;44(10):962-970
Munz M, Chen H, Jockel-Schneider Y, Adam K, Hoffman P, Berger K, Kocher T, Meyle J, Eickholz P, Doerfer C, Laudes M, Uitterlinden A, Lieb W, Franke A, Schreiber S, Offenbacher S, Divaris K, Bruckmann C, Loos BG, Jepsen S, Dommisch H, Schaefer AS
(Siehe online unter https://doi.org/10.1111/jcpe.12749) - Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus. Sci Rep. 2018 Sep 12;8(1):13678
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
(Siehe online unter https://doi.org/10.1038/s41598-018-31980-8) - GWAS for Interleukin-1β levels in gingival crevicular fluid identifies IL37 variants in periodontal inflammation. Nat Commun. 2018 Sep 11;9(1):3686
Offenbacher S, Jiao Y, Kim SJ, Marchesan J, Moss KL, Jing L, Divaris K, Bencharit S, Agler CS, Morelli T, Zhang S, Sun L, Seaman WT, Cowley D, Barros SP, Beck JD, Munz M, Schaefer AS, North KE
(Siehe online unter https://doi.org/10.1038/s41467-018-05940-9) - Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci. Eur J Hum Genet. 2019 Jan;27(1):102-113
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, Ahmad I, 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, Erdmann J, Dommisch H, Schaefer AS
(Siehe online unter https://doi.org/10.1038/s41431-018-0265-5)
