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- Scott, R. A., et al.
(author)
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The link between family history and risk of type 2 diabetes is not explained by anthropometric, lifestyle or genetic risk factors : the EPIC-InterAct study
- 2013
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In: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 56:1, s. 60-69
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Journal article (peer-reviewed)abstract
- Aims/hypothesis: Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.Methods: A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created.Results: A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history.Conclusions/interpretation: Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.
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- den Hoed, M, et al.
(author)
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Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples.
- 2013
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In: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 37:2
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Journal article (peer-reviewed)abstract
- BACKGROUND: Meta-analysis of case-control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.OBJECTIVE: We aimed to validate association of these variants with obesity-related traits in population-based samples.DESIGN: Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r (2)>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age(2) in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.RESULTS: We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (β=0.013 s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).CONCLUSION: Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.
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- Brooke, Hannah L, et al.
(author)
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More of the same or a change of scenery : an observational study of variety and frequency of physical activity in British children.
- 2013
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In: BMC Public Health. - : Springer Science and Business Media LLC. - 1471-2458. ; 13
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Journal article (peer-reviewed)abstract
- BACKGROUND: Physical activity is important for children's health, but successful physical activity promotion is challenging. Whether performing many different types of activities (Variety) is associated with higher physical activity independent of the number of activity sessions (Frequency) is unknown, but this information could inform physical activity promotion and public health strategies in children.METHODS: In the SPEEDY study we measured moderate-to-vigorous intensity physical activity (MVPA; ≥2000 counts/minute) over 7 days using GT1M Actigraph accelerometers in 1700 children from Norfolk, UK (56% girls, Mean ± SD 10.3 ± 0.3 years-old). Children reported participation in 28 leisure-time activities over the previous 7 days. Sex differences in activity participation were assessed using multilevel logistic regression, clustered by school. Associations of log-transformed MVPA with z-score-Variety (number of different activities/week) and z-score-Frequency (sum of all activity sessions/week) were examined using multilevel linear regression, adjusted for age, sex, parental education and age-standardised BMI.RESULTS: Children's activity participation often reflected gender stereotypes. Mean ± SD Variety was 10.8 ± 5.0 activities/week, and Frequency was 24.2±15.0 sessions/week. In separate models lnMVPA had similar strength, positive associations with z-score-Variety and z-score-Frequency (Exp β(95% CI); Variety 1.04(1.02-1.06), Frequency 1.04(1.02-1.06)). lnMVPA was not associated with z-score-Variety independent of z-score-Frequency (Variety 1.01(0.98-1.04), Frequency 1.03(1.00-1.06)).CONCLUSIONS: Future physical activity interventions and public health strategies could allow for gender specific activity preferences and could target both Variety and Frequency of activities participated in by children.
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