Joint Effect of Genetic and Lifestyle Risk Factors on Type 2 Diabetes Risk Among Chinese Men and Women

Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America.
PLoS ONE (Impact Factor: 3.23). 11/2012; 7(11):e49464. DOI: 10.1371/journal.pone.0049464
Source: PubMed


More than 40 genetic susceptibility loci have been reported for type 2 diabetes (T2D). Recently, the combined effect of genetic variants has been investigated by calculating a genetic risk score. We evaluated 36 genome-wide association study (GWAS) identified SNPs in 2,679 T2D cases and 3322 controls in middle-age Han Chinese. Fourteen SNPs were significantly associated with T2D in analysis adjusted for age, sex and BMI. We calculated two genetic risk scores (GRS) (GRS1 with all the 36 SNPs and GRS2 with the 14 SNPs significantly associated with T2D). The odds ratio for T2D with each GRS point (per risk allele) was 1.08 (95% CI: 1.06-1.09) for GRS1 and 1.15 (95% CI: 1.13-1.18) for GRS2. The OR for quintiles were 1.00, 1.26, 1.69, 1.95 and 2.18 (P<0.0001) for GRS1 and 1.00, 1.33, 1.60, 2.03 and 2.80 (P<0.001) for GRS2. Participants in the higher tertile of GRS1 and the higher BMI category had a higher risk of T2D compared to those on the lower tertiles of the GRS1 and of BMI (OR = 11.08; 95% CI: 7.39-16.62). We found similar results when we investigated joint effects between GRS1 and WHR terciles and exercise participation. We finally investigated the joint effect between tertiles of GRSs and a composite high risk score (no exercise participation and high BMI and WHR) on T2D risk. We found that compared to participants with low GRS1 and no high risk factors for T2D, those with high GRS1 and three high risk factors had a higher risk of T2D (OR = 13.06; 95% CI: 8.65-19.72) but the interaction factor was of marginal significance. The association was accentuated when we repeated analysis with the GRS2. In conclusion we found an association between GRS and lifestyle factors, alone and in combination, contributed to the risk of and T2D among middle age Chinese.

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    • "At the group level, in contrast, risk stratification is achievable to some extent by using a genetic risk score (GRS); this is an integrated summary of genetic risk from all the different variants in the genome that GWA studies have identified as predisposing to the disease. The GRS thus calculated has the capacity to highlight patient groups at the top end of the risk distribution78. A higher GRS was shown to be associated with indices of diminished β‐cell function and incidence of diabetes during follow up, gaining predictive ability in comparison with clinical characteristics alone78. Furthermore, lifestyle interventions appear to be effective even among individuals at highest genetic risk78. "
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