Runs of homozygosity are associated with staging of periodontitis in isolated populations

Abstract

Abstract Periodontitis is a common inflammatory disease characterized by a complex etiology, which is the result of a combination of genetic and environmental factors. Genetic variants linked to the periodontitis disease were already investigated, however, little was known regarding the severity of this disease. Recently, long runs of homozygosity (ROH) were associated with several multifactorial diseases. Therefore, in our work, we tried to assess the role of ROH and periodontitis status. We found an association between the excess of homozygosity owing to ROH and staging of periodontitis. More in detail, the total amount of homozygosity owing to ROH is positively associated with an increased severity of periodontitis (P = 0.0001). Regression tree analysis showed the impact of ROH burden in discriminating individuals with mild periodontitis stages I and II and periodontitis stages III and IV (P < 0.001). Furthermore, ROH mapping highlights several regions associated with a severe status of periodontitis (odds ratio > 1). Among them, we found a total of 33 genes. Interestingly, some of these genes were previously associated with granulocyte or platelet measures, both linked to the onset and the progression of periodontal disease. Our results suggest the not only single variants association test could help to risk assessment but even individual genomic features; furthermore, our ROH mapping highlighted the possible role of multiple genes in periodontal development.