Shared genetic architecture between periodontal disease and type 2 diabetes: a large scale genome-wide cross-trait analysis

Abstract

<p><strong>Purpose: </strong>To investigate the relationship between abnormal glucose metabolism, type 2 diabetes (T2D), and periodontal disease (PER) independent of Body Mass Index (BMI), we employed a genome-wide cross-trait approach to clarify the association.</p><p><strong>Methods: </strong>Our study utilized the most extensive genome-wide association studies conducted for populations of European ancestry, including PER, T2D, fasting glucose, fasting insulin, 2-hour glucose after an oral glucose challenge, HOMA-β, HOMA-IR (unadjusted or adjusted for BMI) and HbA1c.</p><p><strong>Results: </strong>With this approach, we were able to identify pleiotropic loci, establish expression-trait associations, and quantify global and local genetic correlations. There was a significant positive global genetic correlation between T2D (r_g = 0.261, p = 2.65 × 10^-13), HbA1c (r_g = 0.182, p = 4.14 × 10^-6) and PER, as well as for T2D independent of BMI (r_g = 0.158, p = 2.34 × 10^-6). A significant local genetic correlation was also observed between PER and glycemic traits or T2D. We also identified 62 independent pleiotropic loci that impact both PER and glycemic traits, including T2D. Nine significant pathways were identified between the shared genes between T2D, glycemic traits and PER. Genetically liability of HOMA-βadjBMI was causally associated with the risk of PER.</p><p><strong>Conclusion: </strong>Our research has revealed a genetic link between T2D, glycemic traits, and PER that is influenced by biological pleiotropy. Notably, some of these links are not related to BMI. Our research highlights an underlying link between patients with T2D and PER, regardless of their BMI.</p>