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

被引:1
作者
Wu, Kevin Chun Hei [1 ]
Liu, Lin [1 ]
Xu, Aimin [1 ,2 ]
Chan, Yap Hang [3 ]
Cheung, Bernard Man Yung [1 ,2 ,4 ]
机构
[1] Univ Hong Kong, Li Ka Shing Fac Med, Dept Med, Pokfulam, Hong Kong, Peoples R China
[2] Univ Hong Kong, State Key Lab Pharmaceut Biotechnol, Pokfulam, Hong Kong, Peoples R China
[3] Univ Hong Kong, Queen Mary Hosp, Div Cardiol, Pokfulam, Hong Kong, Peoples R China
[4] Univ Hong Kong, Inst Cardiovasc Sci & Med, Pokfulam, Hong Kong, Peoples R China
关键词
Periodontal Diseases; Glycemic Control; Type; 2; Diabetes; Insulin Resistance; Genome Wide Association Analysis; MENDELIAN RANDOMIZATION; INSTRUMENTS; OBESITY; EXPRESSION; G6PC2; BIAS;
D O I
10.1007/s12020-024-03766-8
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
PurposeTo 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.MethodsOur 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-beta, HOMA-IR (unadjusted or adjusted for BMI) and HbA1c.ResultsWith 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 (rg = 0.261, p = 2.65 x 10-13), HbA1c (rg = 0.182, p = 4.14 x 10-6) and PER, as well as for T2D independent of BMI (rg = 0.158, p = 2.34 x 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-beta adjBMI was causally associated with the risk of PER.ConclusionOur 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.
引用
收藏
页码:685 / 694
页数:10
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