Linkage disequilibrium analysis of case-control data: an application to generalized aggressive periodontitis

Several studies have shown a role for the involvement of interleukin ( IL)- 1 gene cluster polymorphisms in the risk of periodontal diseases. In the present study, we tested polymorphisms, derived from genes of the IL- 1 cluster, for association with generalized aggressive periodontitis ( GAP) through both allelic association and by constructing a linkage disequilibrium ( LD) map of the 2q13 - 14 disease candidate region. The IL- 1RN ( VNTR) genotype distribution observed was significantly different in GAP and control subjects ( P = 0.019). We also observed some evidence for an association between GAP and the IL- 1B(+3953) polymorphism ( P = 0.039). The pattern of association in the region, represented as an LD map, identifies a recombination hot area between the IL- 1B(+3953) and IL-1B(-511) polymorphisms. Multilocus modelling of association with disease gives a location for the peak association at the IL- 1B(+3953) marker, although support for the peak is not significant. Haplotype analysis identifies a IL- 1B(+3953) - IL-1B(-511) haplotype as having the lowest P- value in the region. Recognition of the presence of a recombination hot area between the IL-1B(+3953) and IL- 1B(-511) polymorphisms will have an important bearing on future efforts to develop higher resolution SNP analysis in this region for both this and other diseases for which this cluster is implicated.