Results of segregation analyses support the possibility that risk of Early Onset Periodontitis (EOP) may be due to a single major gene. Alternatively, several genes of moderate effect may contribute significantly to increasing risk of the disease. We conducted linkage analyses spanning the entire human genome to evaluate these hypotheses. Families with two or more close relatives affected by EOP were ascertained in Virginia, USA and Chile. DNA was extracted from blood and highly polymorphic markers distributed throughout the human genome were typed using the polymerase chain reaction. Linkage analyses were performed using a dominant model of disease transmission which is most strongly supported by the segregation analysis studies, as well as additional analyses based on assumptions of alternative modes of disease gene transmission. We also applied nonparametric methods of inferring linkage and/or linkage disequilibrium which do not require assumptions about the disease's genetic architecture. We have nearly completed these statistical analyses and have found several chromosomal regions with highly statistically significant evidence of linkage or linkage disequilibrium. These include the Interleukin-1 region, which was reported to be associated with levels of severity in adult onset periodontitis. Several of our statistical tests are based on relatively small sample sizes for which statistical theory suggest the estimation of type 1 error may be unreliable when using standard asymptotic methods of inference. To address this, we are employing re-sampling (bootstrap) methods to assess empirically the degree of potential bias in the highly significant p-values obtained in this study.
| Michalowicz, B S; Diehl, S R; Gunsolley, J C et al. (2000) Evidence of a substantial genetic basis for risk of adult periodontitis. J Periodontol 71:1699-707 |
