A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis

Munz, Matthias; Willenborg, Christina; Richter, Gregor; Jockel‐Schneider, Yvonne; Graetz, Christian; Staufenbiel, Ingmar; Wellmann, Jürgen; Berger, Klaus; Krone, Bastian; Hoffmann, Per; Velde, Nathalie van der; Uitterlinden, André G.; Groot, Lisette C. P. G. M. de; Sawalha, Amr H.; Direşkeneli, Haner; Saruhan-Direskeneli, G. her; Güzeldemir-Akçakanat, Esra; Keçeli, Hüseyin Gencay; Laudes, Matthias; Noack, Barbara; Teumer, Alexander; Holtfreter, Birte; Kocher, Thomas; Eickholz, Peter; Meyle, Jörg; Doerfer, Christof; Bruckmann, Corinna; Lieb, Wolfgang; Franke, André; Schreiber, Stefan; Nohutçu, Rahime M.; Erdmann, Jeanette; Loos, Bruno G.; Jepsen, Soeren; Dommisch, Henrik; Schäefer, Arne S.

doi:10.1093/hmg/ddy015

Cited by 41 publications

(88 citation statements)

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“…Most recently, a genome‐wide association approach was used to identify new genetic risk factors for periodontal disease. Different suggestive loci were identified, but only few studies have shown genome‐wide significant results associated to periodontal disease or to related phenotypes . In Schaefer et al, association in a German population between aggressive periodontitis and rs1537415 in the glycosyltransferase gene GLT6D1 was reported .…”

Section: Introductionmentioning

confidence: 99%

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A genome‐wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population

Bevilacqua

Navarra

Pirastu

et al. 2018

J of Periodontal Research

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Background and Objective Periodontitis in one of the most prevalent dental diseases. Despite numerous studies have investigated its aetiopathogenetic factors, few works have focused on its genetic predisposition and most of them took into account only candidate genes. Therefore, we conducted a Genome Wide Association Study in an Italian isolated population aimed at uncovering genetic variants that predispose to this disorder. Methods Diagnosis of chronic periodontitis was made following the criteria of the American Academy of Periodontology. Patients with chronic periodontitis were grouped into different categories: slight, severe, localized and generalized. A control group composed by people without signs of periodontitis or gingivitis was defined. DNA was genotyped using 370k Illumina chips. Linear mixed model regression was used to test the association between each single nucleotide polymorphism (SNP) (independent variable) and the periodontitis status (dependent variable), controlling for confounders sex, age and smoking. The genomic kinship matrix was also used as random effect. Results Four SNPs on the gene EFCAB4B resulted significantly associated to localized periodontitis (P < 5 × 10−8), with the best hit on the rs242016 SNP (P = 1.5 × 10−8). Conclusion We have identified a novel significant association between the EFCAB4B gene and localized periodontitis. These results open a new perspective in the understanding of genetic factors contributing to this common disorder.

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Section: Introductionmentioning

confidence: 99%

“…Recently, Munz et al identified new loci (SIGLEC5 and DEFA1A3) involved in innate and adaptive immunity response as the susceptibility factor for aggressive and chronic periodontitis …”

Section: Introductionmentioning

confidence: 99%

A genome‐wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population

Bevilacqua

Navarra

Pirastu

et al. 2018

J of Periodontal Research

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“…DEFA1A3 SNPs, rs2978951, and rs2738058 successfully showed genomewide significance with P ‐values of 2.06 × 10 −8 (OR of 1.25 and 95% CI of 1.16‐1.35) and 6.78 × 10 −10 (OR of 1.28 and 95% CI of 1.18‐1.38), respectively. Likewise, sialic acid‐binding Ig‐like lectin 5 ( SIGLEC5 ) SNP, rs4284742, showed genomewide significance with a P ‐value of 1.34 × 10 −8 (OR of 1.34 and 95% CI of 1.21‐1.48) (Table ).…”

Section: Defa1a3 and Siglec5mentioning

confidence: 99%

“…A single nucleotide polymorphism (SNP) in interleukin‐1 ( IL‐1 ) was the first identified genetic risk factor for AgP . However, subsequent studies with improved statistical power using samples from homogeneous populations did not validate associations between IL‐1 variants and periodontitis . Subsequently, several genes have been identified as genetic risk factors for AgP, but the full complement of associated genes has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, even additional smaller case‐control samples are enough for validation studies. Until date, only three genes meet these requirements and have been identified as genetic risk factors for AgP with genomewide significance . This review mainly summarizes the current knowledge regarding genetic risk factors for AgP that reach the threshold for genomewide significance.…”

Section: Introductionmentioning

confidence: 99%

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Identification of genetic risk factors of aggressive periodontitis using genomewide association studies in association with those of chronic periodontitis

Masumoto

Kitagaki

Fujihara

et al. 2018

J of Periodontal Research

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To identify the genetic risk factors for aggressive periodontitis (AgP), it is important to understand the progression and pathogenesis of AgP. The purpose of this review was to summarize the genetic risk factors for AgP identified through a case‐control genomewide association study (GWAS) and replication study. The initial studies to identify novel AgP risk factors were potentially biased because they relied on previous studies. To overcome this kind of issue, an unbiased GWAS strategy was introduced to identify genetic risk factors for various diseases. Currently, three genes glycosyltransferase 6 domain containing 1 (GLT6D1), defensin α1 and α3 (DEFA1A3), and sialic acid‐binding Ig‐like lectin 5 (SIGLEC5) that reach the threshold for genomewide significance have been identified as genetic risk factors for AgP through a case‐control GWAS.

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Periodontitis and stroke: A Mendelian randomization study

Gao

et al. 2023

Brain and Behavior

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Background and purpose: Periodontitis has been implicated in the incidence of ischemic stroke. However, the generalizability of results to individuals with different subtypes of periodontitis is unknown. We aimed to investigate the causal relationship of chronic periodontitis (CP) and aggressive periodontitis (AgP) with ischemic stroke and its subtypes in the Mendelian randomization framework. Methods:The genetic proxies of CP were derived from large-scale summary statistics from the UK Biobank datasets (950 cases and 455,398 controls). The genetic associations of AgP were selected from another large genome-wide association study of European ancestry (851 cases and 6836 controls). The instruments of ischemic stroke (34,217 cases and 406,111 controls) and its subtypes were selected from the MEGAS-TROKE consortium of European ancestry. The inverse variant weighted method was performed to determine the causal inference and a comprehensive set of sensitivity analyses to test the robustness of the results. Results:In population-wide genetic analysis, there was no association of genetically predicted AgP (odds ratio [OR], 0.982; 95% confidence interval [CI], 0.956-1.009; p = .197) with ischemic stroke or its subtypes. For patients with CP, there was also no significant causal inference on ischemic stroke (OR, 1.017; 95% CI, 0.992-1.043; p = .184). However, regarding the stroke subtypes, the genetic analysis provided evidence of a causal relationship of CP with cardioembolic stroke (OR, 1.052; 95% CI, 1.002-1.104; p = .042), but not with large artery atherosclerosis (OR, 1.005; 95% CI, 0.944-1.069; p = .875) or small vessel occlusion (OR, 1.039; 95% CI, 0.981-1.101; p = .193). Conclusion:This study suggested that there was a potential causal effect of CP on cardioembolic stroke.

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A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis

Cited by 41 publications

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A genome‐wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population

A genome‐wide association study identifies an association between variants in EFCAB4B gene and periodontal disease in an Italian isolated population

Identification of genetic risk factors of aggressive periodontitis using genomewide association studies in association with those of chronic periodontitis

Periodontitis and stroke: A Mendelian randomization study

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