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.

Download full-text


Available from: Scott M Williams,
9 Reads
  • Source
    • "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. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Type 2 diabetes is one of the most common complex diseases, of which considerable efforts have been made to unravel the pathophysiological mechanisms. Recently, large-scale genome-wide association (GWA) studies have successfully identified genetic loci robustly associated with type 2 diabetes by searching susceptibility variants across the entire genome in an unbiased, hypothesis-free manner. The number of loci has climbed from just three in 2006 to approximately 70 today. For the common type 2 diabetes-associated variants, three features have been noted. First, genetic impacts of individual variants are generally modest; mostly, allelic odds ratios range between 1.06 and 1.20. Second, most of the loci identified to date are not in or near obvious candidate genes, but some are often located in the intergenic regions. Third, although the number of loci is limited, there might be some population specificity in type 2 diabetes association. Although we can estimate a single or a few target genes for individual loci detected in GWA studies by referring to the data for experiments in vitro, biological function remains largely unknown for a substantial part of such target genes. Nevertheless, new biology is arising from GWA study discoveries; for example, genes implicated in β-cell dysfunction are over-represented within type 2 diabetes-associated regions. Toward translational advances, we have just begun to face new challenges - elucidation of multifaceted (i.e., molecular, cellular and physiological) mechanistic insights into disease biology by considering interaction with the environment. The present review summarizes recent advances in the genetics of type 2 diabetes, together with its realistic potential.
    05/2013; 4(3):233-244. DOI:10.1111/jdi.12067
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent studies in both humans and animals suggest that air pollution is an important risk factor for type 2 diabetes mellitus (T2DM). However, the mechanism by which air pollution mediates propensity to diabetes is not fully understood. While a number of epidemiologic studies have shown a positive association between ambient air pollution exposure and risk for T2DM, some studies have not found such a relationship. Experimental studies in susceptible disease models do support this association and suggest the involvement of tissues involved in the pathogenesis of T2DM such as the immune system, adipose, liver, and central nervous system. This review summarizes the epidemiologic and experimental evidence between ambient outdoor air pollution and T2DM. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail:
    Toxicological Sciences 02/2015; 143(2):231-41. DOI:10.1093/toxsci/kfu250 · 3.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetic contributions towards Type 2 diabetes (T2D) have been assessed through association studies across different world populations with inconsistencies. The majority of the T2D susceptibility loci are common across different races or populations but show ethnicityspecific differences. The pathogenesis of T2D involves genetic variants in the candidate genes. The interactions between the genes involved in insulin signaling and secretory pathways are believed to play an important role in determining an individual’s susceptibility towards T2D. Therefore, the present study was initiated to examine the differences, if any, in the contribution of polymorphisms towards T2D susceptibility in the background of different ethnic specifications. The present case–control study included a total of 1216 T2D cases and healthy controls from three ethnic groups (Jat Sikhs, Banias and Brahmins) of North-West India. Polymorphisms were selected on the basis of information available in the literature for INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) in context to T2D. The genotyping was done using PCR– RFLP method. Statistical analysis was done using SPSS 16.0. The analyses revealed that INS (rs689) polymorphism conferred risk towards T2D susceptibility in all the three ethnic groups whereas INSR (rs1799816) polymorphism conferred risk towards T2D in Brahmins only and PP1G.G (rs1799999) polymorphism indicated T2D risk in Jat Sikhs only. Furthermore, interaction analyses indicated the cumulative role of three genetic variants in modulating T2D susceptibility in the three ethnic groups. In conclusion, our results substantiated the evidences for the role of ethnicity in differential susceptibility to T2D in the background of same genetic variants.
    Molecular Genetics and Genomics 08/2015; DOI:10.1007/s00438-015-1099-2 · 2.73 Impact Factor