Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Endocrine. 2024 Aug;85(2):685-694. doi: 10.1007/s12020-024-03766-8. Epub 2024 Mar 9.
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.
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.
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 = 0.261, p = 2.65 × 10), HbA1c (r = 0.182, p = 4.14 × 10) and PER, as well as for T2D independent of BMI (r = 0.158, p = 2.34 × 10). 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.
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.
为了研究葡萄糖代谢异常、2 型糖尿病（T2D）和牙周病（PER）之间的关系，而不受体重指数（BMI）的影响，我们采用全基因组跨性状方法来阐明这种关联。
我们的研究利用了最广泛的针对欧洲血统人群进行的全基因组关联研究，包括 PER、T2D、空腹血糖、空腹胰岛素、口服葡萄糖耐量试验后 2 小时血糖、HOMA-β、HOMA-IR（未调整或按 BMI 调整）和 HbA1c。
通过这种方法，我们能够识别出多效性位点，建立表达-性状关联，并量化全局和局部遗传相关性。T2D（r=0.261，p=2.65×10）、HbA1c（r=0.182，p=4.14×10）和 PER 之间存在显著的正全局遗传相关性，T2D 与 BMI 无关（r=0.158，p=2.34×10）也是如此。PER 与血糖特征或 T2D 之间也观察到显著的局部遗传相关性。我们还鉴定了 62 个独立的多效性位点，这些位点影响 PER 和血糖特征，包括 T2D。在 T2D、血糖特征和 PER 之间的共享基因中发现了 9 个显著的途径。HOMA-βadjBMI 的遗传易感性与 PER 的风险有因果关系。
我们的研究揭示了 T2D、血糖特征和 PER 之间受生物学多效性影响的遗传联系。值得注意的是，其中一些联系与 BMI 无关。我们的研究强调了 T2D 患者和 PER 患者之间的潜在联系，无论他们的 BMI 如何。
