Genetic power of a Brazilian three-generation family with generalized aggressive periodontitis

Abstract

Aggressive periodontitis is a multifactorial disease with strong familial aggregation. Genetic linkage analysis is a method to localize causative or predisposing genes along the chromosome, thus helping to unravel important pathogenic pathways. Prior to applying this method, however, it is essential to estimate the power of the study design. The aim of this study was to estimate the power of a large Brazilian family with generalized aggressive periodontitis (GAgP) for future linkage analysis. A three-generation family was seen at the Dental School of the Federal University of Bahia. A full-mouth periodontal probing at 6 sites/tooth was performed in all 23 family members. Five out of 10 siblings were affected with GAgP. A parametric simulation (theta = 0) was performed on 100 replicates using the statistical software SLINK for linkage analysis. The linkage LOD score criteria for complex diseases described by Haines was adopted. There was maximum expected LOD scores of 3.56 and 3.48 at penetrance rate F = 0.98, and both studied phenocopy rates p=0.0 and p=0.02, respectively. The analyzed family showed statistical power for future genetic linkage analysis of candidate genes to GAgP.

Aggressive periodontitis: case definition and diagnostic criteria

“…Baer (15) described a pattern where aggressive periodontitis tends to cluster within families. Findings in other studies corroborate the familial pattern of this disease (47, 52). Several mechanisms of increased predisposition to the disease by genetic factors have been proposed (39, 42, 68).…”

GC Gene Polymorphisms and Vitamin D-Binding Protein Levels Are Related to the Risk of Generalized Aggressive Periodontitis

“…Recent studies of aggressive periodontitis pay more attention to single nucleotide polymorphisms (SNPs) because the disease has significant familial aggregation, which indicates that genetic predisposition may be an important etiological factor of aggressive periodontitis [16, 17]. DBP is encoded by the GC gene, which is located on chromosome 4 (4q11–q13) and coded by 1690 nucleotides.…”

Genetic power of a brazilian three-generation family with generalized aggressive periodontitis. II

“…As previously described (12), given the age dependence of the expression of periodontitis concerning the time needed for the sequels to accumulate, family members under the age of 14 were classified as unknown phenotype in order to avoid misclassification of the phenotype in the study model (14). None of the family members had ever received any information about their periodontal status or had ever undergone periodontal treatment prior to the present study.…”

“…A s p r e v i o u s l y described (12), the statistical analysis involved the estimation of the probability for reaching a LOD score of Z ≥ 3. An autosomal dominant inheritance mode was assumed.…”

“…An essential step prior to performing linkage analyses is to estimate the power of the study design in order to determine whether the available pedigree information is sufficient to allow the detection of gene(s) underlying the trait(s) of interest and to optimize the cost of the study (11). In a previous report, we described the power in a Brazilian threegeneration family to detect linkage to candidate gene(s) to generalized aggressive periodontitis (GAgP) (12). As one more large family seen at the Dental School of the Federal University of Bahia has been diagnosed with GAgP, and given the relevance of confirming genetic findings on different datasets in a multistage genetic mapping, the aim of the present study was to estimate the power of this new family for future genetic linkage analysis of candidate gene(s) to GAgP.…”