Association of genetic predisposition to obesity with type 2 diabetes risk in Han Chinese individuals

Abstract

Aims/hypothesis Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMIassociated 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 BMIincreasing 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. ) 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.

Newly identified set of obesity‐related genotypes and abdominal fat influence the risk of insulin resistance in a Korean population

“…Our findings are in line with the results of some previous studies in which the obesity‐risk alleles were associated with IR . In contrast, several studies showed that obesity‐risk alleles were more closely associated with markers of beta cell function than IR in Asian populations . The underlying suggested cause of the discrepancy between other populations was ethnicity, which might reflect the difference in the etiological role of obesity in the development of type 2 diabetes .…”

“…[3][4][5][6] In contrast, several studies showed that obesity-risk alleles were more closely associated with markers of beta cell function than IR in Asian populations. 16,17 The underlying suggested cause of the discrepancy between other populations was ethnicity, which might reflect the difference in the etiological role of obesity in the development of type 2 diabetes. 17,18 However, in the present study, the Korean population showed that IR had a stronger impact than insulin secretion, suggesting that a genetic susceptibility to obesity may affect IR in the Korean population.…”

Metabolic stress-induced joint inflammation and osteoarthritis

“…environment seem key factors in the onset and progression of metabolic336 diseases, but obesity and type 2 diabetes are also subject to genetic susceptibility, and risk of 337 OA onset in obese subjects could be affected by common genetic factors128,129 . Since 2007, 338 the single nucleotide polymorphism in the fat mass and obesity-associated (FTO) gene has with risk of excess fat mass and obesity in several populations, so 340 investigating this gene in OA could be of interest130 .…”

Genetic polymorphisms associated with pediatric‐onset type 2 diabetes: A family‐based transmission disequilibrium test and case‐control study

“…On the other hand, the TDT and case‐control analysis suggest that GLIS3 /rs7034200 and VEGFA /rs6905288 are associated with T2D independently of the obesity status. This adiposity independent effect has been reported for other obesity‐associated genetic variants …”

“…In addition, some obesity susceptibility loci also increase the risk of T2D independent of body mass index (BMI) or could be mediated by obesity‐predisposing effect . The information about the contribution of obesity‐susceptibility variants to pediatric‐onset T2D is scarce.…”