Abstract
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.
Highlights
Type 2 diabetes (T2D) is a complex disease affecting more than a billion people worldwide
We evaluated the association between reported SNP from genome-wide association study (GWAS) with T2D using data from a GWAS study of T2D of middle age women and from a nested case control study from two population based cohorts of middle age men and women living in urban Shanghai, China and calculated genetic risk scores (GRSs) with T2D susceptibility markers
We looked at joint associations between genetic risk score tertiles with tertiles of body mass index (BMI), waist to hip ratio (WHR) and exercise participation and with a composite lifestyle high risk score including high BMI, high WHR and no exercise participation
Summary
Type 2 diabetes (T2D) is a complex disease affecting more than a billion people worldwide. Over the last two decades, China, like many other Asian countries, has experienced a dramatic increase in T2D incidence Both genetic and environmental factors contribute to the development of T2D. Some data is available on the joint effects of common genetic variants on the risk of T2D [9,10,11,12,13,14]. Most of these studies have not taken into consideration interactions between genetic risk and environmental factors. We looked at joint associations between genetic risk score tertiles with tertiles of body mass index (BMI), waist to hip ratio (WHR) and exercise participation and with a composite lifestyle high risk score including high BMI, high WHR and no exercise participation
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