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- Graff, M., et al.
(författare)
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Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults
- 2017
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Ingår i: PLoS Genet. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.
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| 3. |
- Walford, G. A., et al.
(författare)
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Genome-wide association study of the modified stumvoll insulin sensitivity index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci
- 2016
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Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 65:10, s. 3200-3211
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: Rs13422522 (NYAP2; P = 8.87 × 10-11), rs12454712 (BCL2; P = 2.7 × 10-8), and rs10506418 (FAM19A2; P = 1.9 × 10-8). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci. © 2016 by the American Diabetes Association.
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| 4. |
- Eliraqi, Galal M., et al.
(författare)
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Intensive multifactorial treatment modifies the effect of family history of diabetes on glycaemic control in people with Type 2 diabetes: a post hoc analysis of the ADDITION-Denmark randomized controlled trial
- 2015
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Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 32:8, s. 1085-1089
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Tidskriftsartikel (refereegranskat)abstract
- AimTo investigate whether intensive multifactorial treatment can reverse the predisposed adverse phenotype of people with Type 2 diabetes who have a family history of diabetes. MethodsData from the randomized controlled trial ADDITION-Denmark were used. A total of 1441 newly diagnosed patients with diabetes (598 with family history of diabetes) were randomized to intensive treatment or routine care. Family history of diabetes was defined as having one parent and/or sibling with diabetes. Linear mixed-effects models were used to assess the changes in risk factors (BMI, waist circumference, blood pressure, lipids and HbA(1c)) after 5years of follow-up in participants with and without a family history of diabetes. An interaction term between family history of diabetes and treatment group was included in the models to test for a modifying effect of the intervention. All analyses were adjusted for age, sex, baseline value of the risk factor and general practice (random effect). ResultsAt baseline, participants with a family history of diabetes were younger and had a 1.1 mmol/mol (0.1%) higher HbA(1c) concentration at the time of diagnosis than those without a family history of diabetes. Family history of diabetes modified the effect of the intervention on changes in HbA(1c) levels. In the group receiving routine care, participants with a family history of diabetes experienced an improvement in HbA(1c) concentration that was 3.3mmol/mol (0.3%) lower than the improvement found in those without a family history of diabetes after 5years of follow-up. In the intensive treatment group, however, there was no difference in HbA(1c) concentrations between participants with and without a family history of diabetes after 5years of treatment. ConclusionsIntensive treatment of diabetes may partly remove the adverse effects of family history of diabetes on glycaemic control. The effect of this improvement on long-term diabetic complications warrants further investigation. What's new? People with Type 2 diabetes who have a family history of diabetes have worse glycaemic control than those with Type 2 diabetes without a family history of diabetes. Intensive multifactorial treatment, but not routine clinical care, partly removes the adverse effects of family history of diabetes on glycaemic control.
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