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Exploring causal associations of alcohol with cardiovascular and metabolic risk factors in a Chinese population using Mendelian randomization analysis.
Taylor, AE, Lu, F, Carslake, D, Hu, Z, Qian, Y, Liu, S, Chen, J, Shen, H, Smith, GD
Scientific reports. 2015;:14005
Abstract
Observational studies suggest that moderate alcohol consumption may be protective for cardiovascular disease, but results may be biased by confounding and reverse causality. Mendelian randomization, which uses genetic variants as proxies for exposures, can minimise these biases and therefore strengthen causal inference. Using a genetic variant in the ALDH2 gene associated with alcohol consumption, rs671, we performed a Mendelian randomization analysis in 1,712 diabetes cases and 2,076 controls from Nantong, China. Analyses were performed using linear and logistic regression, stratified by sex and diabetes status. The A allele of rs671 was strongly associated with reduced odds of being an alcohol drinker in all groups, but prevalence of alcohol consumption amongst females was very low. The A allele was associated with reduced systolic and diastolic blood pressure and decreased total and HDL cholesterol in males. The A allele was also associated with decreased triglyceride levels, but only robustly in diabetic males. There was no strong evidence for associations between rs671 and any outcomes in females. Our results suggest that associations of alcohol consumption with blood pressure and HDL-cholesterol are causal. Alcohol also appeared to have adverse effects on triglyceride levels, although this may be restricted to diabetics.
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Genetic variant in fat mass and obesity-associated gene associated with type 2 diabetes risk in Han Chinese.
Qian, Y, Liu, S, Lu, F, Li, H, Dong, M, Lin, Y, Du, J, Lin, Y, Gong, J, Jin, G, et al
BMC genetics. 2013;:86
Abstract
BACKGROUND Genome-wide association study (GWAS) has identified that rs8050136 C/A polymorphism in fat mass and obesity-associated gene (FTO) was associated with the risk of type 2 diabetes (T2D) in Europeans. But this association was abolished after adjustment for body mass index (BMI), suggesting that the effect of rs8050136 on T2D risk might be mediated by BMI in Europeans. However, the findings in subsequent studies were inconsistent among Asian populations. To determine whether rs8050136 polymorphism in FTO is independently associated with the risk of T2D in Chinese, we conducted a case-control study with 2,925 T2D patients and 3,281 controls in Han Chinese. RESULTS Logistic regression revealed that the A allele of rs8050136 was significantly associated with an increased risk of T2D, independent of BMI (odds ratio (OR) = 1.17, 95% confidence interval (95% CI) = 1.03-1.32, p = 0.016). Meta-analysis containing 10 reported studies and our data with a total of 15,819 cases and 18,314 controls further confirmed the association between rs8050136 polymorphism and T2D risk in East Asians (OR = 1.13, 95% CI = 1.07-1.19). CONCLUSIONS Our findings indicate that the genetic variant in FTO may contribute to T2D risk in Han Chinese and rs8050136 polymorphism may be a genetic marker for T2D susceptibility.
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Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.
Li, H, Kilpeläinen, TO, Liu, C, Zhu, J, Liu, Y, Hu, C, Yang, Z, Zhang, W, Bao, W, Cha, S, et al
Diabetologia. 2012;(4):981-95
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Abstract
AIMS/HYPOTHESIS FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
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Meta-analysis added power to identify variants in FTO associated with type 2 diabetes and obesity in the Asian population.
Liu, Y, Liu, Z, Song, Y, Zhou, D, Zhang, D, Zhao, T, Chen, Z, Yu, L, Yang, Y, Feng, G, et al
Obesity (Silver Spring, Md.). 2010;(8):1619-24
Abstract
Several common variants in the intron 1 of FTO (fat mass and associated obesity) gene have been reliably associated with BMI and obesity in European populations. We analyzed two variants (rs9939609 and rs8050136) in 4,189 Chinese Han individuals and conducted a meta-analysis of published studies in Asian population to investigate whether these variants are associated with type 2 diabetes (T2D) and obesity in Asian population. In this study, both the minor allele A of rs9939609 and the minor allele A of rs805136 were associated with increased risk of T2D, independent of measures of BMI; the odds ratios (ORs) per copy of the risk allele were 1.19 for rs9939609 (95% confidence interval (CI), 1.04-1.37; P = 0.01) and 1.22 for rs8050136 (95% CI, 1.07-1.40; P = 0.004) after adjusting for age, sex, and BMI. Our results also showed association with risk of obesity (rs9939609: OR = 1.39 (95% CI 1.04-1.85), P = 0.02; rs8050136: OR = 1.45 (95% CI 1.09-1.93), P = 0.01) but no association with overweight. These results were consistent with the pooled results from our meta-analysis study (for diabetes, rs8050136, P = 1.3 x 10(-3); rs9939609, P = 9.8 x 10(-4); for obesity, rs8050136, P = 2.2 x 10(-7); rs9939609, P = 9.0 x 10(-9)). Our findings indicate that the two variants (rs9939609 and rs8050136) in the FTO gene contribute to obesity and T2D in the Asian populations.