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

Abstract

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.

Genomics of periodontal disease and tooth morbidity

“…Other studies have implicated numerous loci without reaching genome‐wide statistical significance levels and/or demonstrating replication in an independent cohort. For example, a recent study among a small Italian population reported associations between EFCAB4B polymorphisms (rs242016 showing the strongest evidence of association) and localized periodontitis …”

“…For example, a recent study among a small Italian population reported associations between EFCAB4B polymorphisms (rs242016 showing the strongest evidence of association) and localized periodontitis. 24 Interestingly, several loci have been highlighted as showing suggestive evidence of association (with P values typically ranging between 5 × 10 −6 and 5 × 10 −8 ) in more than one (independent) genome-wide association study and thus warrant attention. A prime example is SIGLEC5 (rs12461706), which was reported in a recent study of aggressive periodontitis 30 and was the only locus that met genome-wide statistical significance criteria in a large, consortium meta-analysis of chronic periodontitis that combined clinical and self-reported data.…”

“…Some of the limitations of genome-wide association studies for periodontitis are related to the sample size of the study and the inherent complexity in defining the trait. A commonly cited limitation in the periodontal genome-wide association study literature is the relatively modest sample sizes of individual studies compared with reports for other common complex diseases, ranging between a few hundred 24,28 and up to 10 000-17 000 participants. 23,26 This has been somewhat overcome by the establishment of the Gene-Lifestyle Interactions and Dental Endpoints consortium 56 and a recent report of periodontitis and dental caries genome-wide association studies among over half a million individuals.…”

Genome-wide Association Study of Periodontal Pocketing in Finnish Adults

“…Sanders et al (2017) found an association with TSNAXDISC1 noncoding mRNA (lead signal: rs149133391) in a large population of Hispanics and Latinos and the variant was replicated independently in an African-American but not in a European-American sample. In a genetically isolated population in Italy, four SNPs in the EFCAB4B gene (rs242016, rs242014, rs10491972, and rs242002) were found to be signi cantly associated with localized periodontitis but the ndings have not been replicated so far [18].…”

“…A number of studies have investigated genomewide associations of different periodontitis phenotypes [2,8]. In terms of the GWA approach in chronic periodontitis, several studies using various case de nitions and populations of different ethnic origins have been published [9][10][11][12][13][14][15][16][17][18][19][20][21]. Only a few of these studies reported associations on the level of stringent genome-wide signi cance level (p-value < 5 × 10 − 8 ) [16,18,21,22].…”