title: Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals.
abstract: OBJECTIVE
  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
  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.
authors: Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, 320 Yue-Yang Rd, Shanghai, 200031, People's Republic of China.
authors: Jingwen
authors: J
authors: Zhu
authors: Geng
authors: G
authors: Zong
authors: Ling
authors: L
authors: Lu
authors: Wei
authors: W
authors: Gan
authors: Linong
authors: L
authors: Ji
authors: Renming
authors: R
authors: Hu
authors: Xingwang
authors: X
authors: Ye
authors: Liang
authors: L
authors: Sun
authors: Ruth J F
authors: RJ
authors: Loos
authors: Huaixing
authors: H
authors: Li
authors: Xu
authors: X
authors: Lin
mesh_terms: D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans