| 1. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 2. |
- Varga, Tibor V., et al.
(författare)
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Organizational Justice and Long-term Metabolic Trajectories : A 25-Year Follow-up of the Whitehall II Cohort
- 2022
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:2, s. 398-409
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Tidskriftsartikel (refereegranskat)abstract
- Context: Organizational justice has been linked to lower risk of several chronic conditions among employees, but less is known about the long-term mechanisms underlying this risk reduction.Objective: To assess whether self-reported organizational justice is associated with individual and composite long-term metabolic trajectories.Design: Twenty-five-year follow-up of the Whitehall II prospective cohort study.Setting: Middle-aged public servants from the United Kingdom.Participants: Data on 8182 participants were used.Main Outcome Measures: Levels of 11 anthropometric, glycemic, lipid, and blood pressure biomarkers were measured at 5 timepoints (1991–2013). We used generalized estimating equations and group-based trajectory modeling to investigate the relationship between organizational justice and biomarker trajectories.Results: High vs low organizational justice were associated with lower waist (−1.7 cm) and hip (−1 cm) circumference, body mass index (−0.6 kg/m2), triglycerides (−1.07 mmol/L), and fasting insulin (−1.08 µIU/mL) trajectories. Two latent metabolic trajectory clusters were identified: a high- and a low-risk cluster. High organizational justice (vs low) were associated with belonging to the low-risk cluster (pooled odds ratio = 1.47). The low-risk cluster demonstrated lower baseline levels of most biomarkers and better glycemic control, whereas the high-risk cluster showed higher baseline levels of most biomarkers, glycemic deterioration, but also greater improvements in lipid levels over time.Conclusions: People with high organizational justice had more favorable long-term cardiometabolic biomarker patterns than those with low organizational justice, indicating a potential mechanism contributing to the lower risk of chronic diseases in the first group. Further intervention studies are warranted to determine whether improvement of organizational justice might improve long-term health.
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