Abstract：
AIMS/HYPOTHESIS:Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations. METHODS:In this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMI-increasing alleles of these variants were tested for associations with type 2 diabetes and related glycaemic traits in 1,873 cases of type 2 diabetes and 1,839 controls in Han Chinese individuals. Logistic and linear regression analyses were performed to determine the association with type 2 diabetes risk or related glycaemic traits, respectively, under an additive model with or without adjustment for BMI. RESULTS:The GRS was significantly associated with increased BMI (β [SE] 0.070 [0.016]; p = 1.33 × 0(-5)) in the overall population. Each additional BMI-increasing allele in the GRS increased type 2 diabetes risk by 1.029-fold (95% CI 1.008, 1.050; p = 0.0056) without adjustment for BMI, and the association was slightly attenuated after adjustment for BMI (OR 1.022; 95% CI 1.002, 1.043; p = 0.035). In non-diabetic controls, the GRS was also associated with HOMA of beta cell function (HOMA-B) with adjustment for BMI (β [SE] -0.876 [0.345]; p = 0.011). Notably, the association of GRS with type 2 diabetes was abolished after adjusting for HOMA-B (OR 1.012; 95% CI 0.986, 1.039; p = 0.380). CONCLUSIONS/INTERPRETATION:Our results suggested that genetic predisposition to obesity leads to increased risk of type 2 diabetes, independent of BMI and partly through impaired beta cell function.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Zhu J,Zong G,Lu L,Gan W,Ji L,Hu R,Ye X,Sun L,Loos RJ,Li H,Lin Xdoi
10.1007/s00125-014-3308-7subject
Has Abstractpub_date
2014-09-01 00:00:00pages
1830-3issue
9eissn
0012-186Xissn
1432-0428journal_volume
57pub_type
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